Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more

Annual Review of Immunology

Volumn 21, Issue , 2003, Pages 71-105

  Marsden, Vanessa S ^a   Strasser, Andreas ^a  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

Cell survival; Fas; Lymphocyte development; Myeloid development; Repertoire selection

Indexed keywords

BH3 PROTEIN; CASPASE; PROTEIN; PROTEIN BCL 2; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG;

APOPTOSIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE ACTIVATION; BONE MARROW CELL; CELL DEATH; CELL MATURATION; CELL SELECTION; CELL SURVIVAL; DENDRITIC CELL; ENZYME ACTIVITY; FOLLICULAR LYMPHOMA; GRANULOCYTE; HOMEOSTASIS; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNE SYSTEM; LEUKEMOGENESIS; LYMPHOCYTE FUNCTION; LYMPHOID CELL; LYMPHOID ORGAN; LYMPHOPROLIFERATIVE DISEASE; MACROPHAGE; MAST CELL; MOLECULAR DYNAMICS; NONHUMAN; PATHOGENESIS; PLASMACYTOMA; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; SEPSIS; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; VIRUS INFECTION; ANIMAL; B LYMPHOCYTE; CYTOLOGY; GROWTH, DEVELOPMENT AND AGING; IMMUNOLOGY;

ANIMALS; APOPTOSIS; B-LYMPHOCYTES; CASPASES; HUMANS; IMMUNE SYSTEM; MYELOID CELLS; PROTO-ONCOGENE PROTEINS C-BCL-2; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 0038021272     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.immunol.21.120601.141029     Document Type: Review

References (257)

1. Vaux DL, Strasser A. 1996. The molecular biology of apoptosis. Proc. Natl. Acad. Sci. USA 93:2239-44
2. Kerr JFR, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-57
3. Wyllie AH, Kerr JFR, Currie AR. 1980. Cell death: the significance of apoptosis. Int. Rev. Cytol. 68:251-306
4. Hengartner MO, 2000. The biochemistry of apoptosis. Nature 407:770-76
5. Savill J, Fadok V. 2000. Corpse clearance defines the meaning of cell death. Nature 407:784-88
6. Thornberry NA, Lazebnik Y. 1998. Caspases: enemies within. Science 281:1312-16
7. Salvesen GS, Dixit VM. 1999. Caspase activation: the induced-proximity model. Proc. Natl. Acad. Sci. USA 96:10964-67
8. Verhagen AM, Coulson EJ, Vaux DL. 2001. Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol. 2:1-10
9. Strasser A, O'Connor L, Dixit VM, 2000. Apoptosis signaling. Annu. Rev. Biochem. 69:217-45
10. Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH, Peter ME. 1995. Cytotoxicity-dependent APO-1 (Fas/CD95) - associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14:5579-88
11. Boldin MP, Varfolomeev EE, Pancer Z, Mett IL, Camonis JH, Wallach D. 1995. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J. Biol. Chem. 270:7795-98
12. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM. 1995. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505-12
13. Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM. 1996. FLICE, a novel FADD homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/Apo-1) death-inducing signaling complex. Cell 85:817-27
14. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. 1996. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85:803-15
15. Newton K, Harris AW, Bath ML, Smith KGC, Strasser A. 1998. A dominant interfering mutant of FADD/Mort1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J. 17:706-18
16. Zhang JK, Cado D, Chen A, Kabra NH, Winoto A. 1998. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature 392:296-300
17. Yeh WC, Pompa JL, McCurrach ME, Shu HB, Elia AJ, Shahinian A, Ng M, Wakeham A, Khoo W, Mitchell K, El-Deity WS, Lowe SW, Goeddel DV, Mak TW. 1998. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science 279:1954-58
18. Smith KGC, Strasser A, Vaux DL. 1996. CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease. EMBO J. 15:5167-76
19. Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D. 1998. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apol, and DR3 and is lethal prenatally. Immunity 9:267-76
20. Thome M, Tschopp J. 2001. Regulation of lymphocyte proliferation and death by FLIP. Nat. Rev. Immunol. 1:50-58
21. Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer J-L, Schröter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J. 1997. Viral FLI-CE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517-21
22. Krueger A, Schmitz I, Baumann S, Krammer PH, Kirchhoff S. 2001. Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex. J. Biol. Chem. 276:20633-40
23. Kataoka T, Schroter M, Hahne M, Schneider P, Irmler M, Thome M, Froelich CJ, Tschopp J. 1998. FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma irradiation. J. Immunol. 161:3936-42
24. Strasser A, Harris AW, Huang DCS, Krammer PH, Cory S. 1995. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 14:6136-47
25. L. Proc. Natl. Acad. Sci. USA 96:14871-76
26. Villunger A, O'Reilly LA, Holler N, Adams JM, Strasser A. 2000. Fas ligand, Bcl-2, G-CSF and p38 MAPK: regulators of distinct cell death and survival pathways in granulocytes. J. Exp. Med. 192:647-57
27. Vaux DL, Cory S, Adams JM. 1988. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c- myc to immortalize pre-B cells. Nature 335:440-42
28. Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ. 1991. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67:879-88
29. Strasser A, Harris AW, Cory S. 1991. Bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67:889-99
30. Bouillet P, Metcalf D, Huang DCS, Tarlinton DM, Kay TWH, Köntgen F, Adams JM, Strasser A. 1999. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735-38
31. Hildeman DA, Zhu Y, Mitchell TC, Bouillet P, Strasser A, Kappler J, Mawack P. 2002. Activated T cell death in vivo mediated by pro-apoptotic Bcl-2 family member, Bim. Immunity 16:759-67
32. Lindsten T, Ross AJ, King A, Zong W, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K, Chen Y, Wei M, Eng VM, Adelman DM, Simon MC, Ma A, Golden JA, Evan G, Korsmeyer SJ, MacGregor GR, Thompson CB. 2000. The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues. Mol. Cell 6:1389-99
33. Li HL, Zhu H, Xu C-J, Yuan JY. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491-501
34. Luo X, Budilhardjo I, Zou H, Slaughter C, Wang XD. 1998. Bid, a Bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481-90
35. Adams JM, Cory S. 1998. The Bcl-2 protein family: arbiters of cell survival. Science 281:1322-26
36. Choi SS, Park IC, Yun JW, Sung YC, Hong SI, Shin HS. 1995. A novel bcl-2 related gene, bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow. Oncogene 11:1693-98
37. Lin EY, Orlofsky A, Wang H-G, Reed JC, Prystowsky MB. 1996. A1, a bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood 87:983-92
38. Gibson L, Holmgreen S, Huang DCS, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S. 1996. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 13:665-75
39. Boise LH, Gonzalez -Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB. 1993. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74:597-608
40. Song Q, Kuang Y, Dixit VM, Vincenz C. 1999. Boo, a novel negative regulator of cell death, interacts with Apaf-1. EMBO J. 18:167-78
41. Inohara N, Gourley TS, Carrio R, Muñiz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Nuñez G. 1998. Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death. J. Biol. Chem. 273:32479-86
42. Ke N, Godzik A, Reed JC. 2001. Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak. J. Biol. Chem. 276:12481-84
43. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. 1993. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to bcl-2. Proc. Natl. Acad. Sci. USA 90:3516-20
44. Lithgow T, van Driel R, Bertram JF, Strasser A. 1994. The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum and the outer mitochondrial membrane. Cell Growth Differ. 5:411-17
45. Oltvai ZN, Milliman CL, Korsmeyer SJ. 1993. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609-19
46. Chittenden T, Harrington EA, O' Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC. 1995. Induction of apoptosis by the Bcl-2 homologue Bak. Nature 374:733-36
47. Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ. 1995. Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374:736-39
48. Farrow SN, White JHM, Martinou I, Raven T, Pun K-T, Grinham CJ, Martinou J-C, Brown R. 1995. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature 374:731-33
49. Hsu SY, Hsueh AJW. 1998. A splicing variant of the Bcl-2 member Bok with a truncated BH3 domain induces apoptosis but does not dimerize with antiapoptotic Bcl-2 proteins in vitro. J. Biol. Chem. 273:30139-46
50. L. J. Biol. Chem. 273:8705-10
51. Guo B, Godzik A, Reed JC. 2001. Bcl-G, a novel pro-apoptotic member of the Bcl-2 family. J. Biol. Chem. 276:2780-85
52. Suzuki M, Youle RJ, Tjandra N. 2000. Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103:645-54
53. Huang DCS, Strasser A. 2000. BH3-only proteins - essential initiators of apoptotic cell death. Cell 103:839-42
54. L and Bcl-2, displaces Bax and promotes cell death. Cell 80:285-91
55. Wang K, Yin X-M, Chao DT, Milliman CL, Korsmeyer SJ. 1996. BID: a novel BH3 domain-only death agonist. Genes Dev. 10:2859-69
56. Boyd JM, Gallo GJ, Elangovan B, Houghton AB, Malstrom S, Avery BJ, Ebb RG, Subramanian T, Chittenden T, Lutz RJ, Chinnadurai G. 1995. Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins. Oncogene 11:1921-28
57. O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DCS. 1998. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 17:384-95
58. Hegde R, Srinivasula SM, Ahmad M, Femandes-Alnemri T, Alnemri ES. 1998. Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist. J. Biol. Chem. 273:7783-86
59. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DCS, Strasser A. 2001. Bmf: a pro-apoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293:1829-32
60. Imaizumi K, Tsuda M, Imai Y, Wanaka A, Takagi T, Tohyama M. 1997. Molecular cloning of a novel polypeptide, DP5, induced during programmed neuronal death. J. Biol. Chem. 272:18842-48
61. L. EMBO J. 16:1686-94
62. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. 2000. Noxa, a BH3-only member of the bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053-58
63. Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T. 2001. Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proc. Natl. Acad. Sci. USA 98:11318-23
64. Nakano K, Vousden KH. 2001. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell 7:683-94
65. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B. 2001. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell 7:673-82
66. Green DR, Reed JC. 1998. Mitochondria and apoptosis. Science 281:1309-11
67. Gross A, McDonnell JM, Korsmeyer SJ. 1999. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899-911
68. Wang X. 2001. The expanding role of mitochondria in apoptosis. Genes Dev. 15:2922-33
69. Ellis RE, Yuan J, Horvitz HR. 1991. Mechanisms and functions of cell death. Annu. Rew. Cell Biol. 7:663-98
70. Bouillet P, Purton JF, Godfrey DI, Zhang L-C, Coultas L, Puthalakath H, Pellegrini M, Cory S, Adams JM, Strasser A. 2002. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415:922-26
71. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. 1997. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of Caspase-3. Cell 90:405-13
72. L. J. Cell Biol. 149:623-34
73. Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB. 2001. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15:1481-86
74. L sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8:705-11
75. Hengartner MO, Horvitz HR. 1994. Activation of C. elegans cell death protein CED-9 by an amino-acid substitution in a domain conserved in Bcl-2. Nature 369:318-20
76. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. 2002. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem. 277:13,430-37
77. Dorstyn L, Read S, Cakouros D, Huh JR, Hay BA, Kumar S. 2002. The role of cytochrome c in caspase activation in Drosophila melanogaster cells. J. Cell. Biol. 156:1089-98
78. Zimmermann KC, Ricci JE, Droin NM, Green DR. 2002. The role of ARK in stress-induced apoptosis in Drosophila cells. J. Cell. Biol. 156:1077-87
79. Conradt B, Horvitz HR. 1999. The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell 98:317-27
80. Puthalakath H, Strasser A. 2002. Keeping killers on a tight leash: transcriptional and post-translational control of the proapoptotic activity of BH3-only proteins. Cell Death Differ. 9:505-12
81. Puthalakath H, Huang DCS, O'Reilly LA, King SM, Strasser A. 1999. The pro-apoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3:287-96
82. L. Cell 87:619-28
83. Blume-Jensen P, Janknecht R, Hunter T. 1998. The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr. Biol. 8:779-82
84. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. 1997. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231-41
85. Harada H, Becknell B, Wilm M, Mann M, Huang LJ, Taylor SS, Scott JD, Korsmeyer SJ. 1999. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Mol. Cell 3:413-22
86. del Peso L, González-Garcia M, Page C, Herrera R, Nuñez G. 1997. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278:687-89
87. Putcha GV, Harris CA, Moulder KL, Easton RM, Thompson CB, Johnson EM Jr. 2002. Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice. J. Cell. Biol. 157:441-53
88. Bouillet P, Cory S, Zhang L-C, Strasser A, Adams JM. 2001. Degenerative disorders caused by Bcl-2 deficiency are prevented by loss of its BH3-only antagonist Bim. Dev. Cell 1:645-53
89. Yuan JY, Horvitz HR. 1990. The Caenorhabditis elegans genes ced-3 and ced-4 act autonomously to cause programmed cell death. Dev. Biol. 138:33-41
90. Nicholson DW. 1999. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6:1028-42
91. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G. 1999. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441-46
92. Li LY, Luo X, Wang X. 2001. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95-99
93. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314-17
94. Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S. 1994. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76:969-76
95. McDonnell TJ, Deane N, Platt FM, Nuñez G, Jaeger U, McKearn JP, Korsmeyer SJ. 1989. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 57:79-88
96. Strasser A, Whittingham S, Vaux DL, Bath ML, Adams JM, Cory S, Harris AW. 1991. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl. Acad. Sci. USA 88:8661-65
97. Ogilvy S, Metcalf D, Print CG, Bath ML, Harris AW, Adams JM. 1999. Constitutive bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival. Proc. Natl. Acad. Sci. USA 96:14943-48
98. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ. 1993. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229-40
99. Nakayama K, Nakayama K-I, Negishi I, Kuida K, Sawa H, Loh DY. 1994. Targeted disruption of bcl-2ab in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc. Natl. Acad. Sci. USA 91:3700-4
100. Matsuzaki Y, Nakayama K-I, Nakayama K, Tomita T, Isoda M, Loh DY, Nakauchi H. 1997. Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem cell. Blood 89:853-62
101. Motoyama N, Wang FP, Roth KA, Sawa H, Nakayama K, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S, Loh DY. 1995. Massive cell death of immature hematopoietic cells and neurons in Bcl-x deficient mice. Science 267:1506-10
102. Tamura A, Katsumata M, Greene MI, Yui K. 1996. Inhibition of apoptosis and augmentation of lymphoproliferation in bcl-2 transgenic Fas/Fas ligand-defective mice. Cell. Immunol. 168:220-28
103. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS-S, Flavell RA. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin-1b converting enzyme. Science 267:2000-3
104. Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A, Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL, Yuan J. 1998. Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev. 12:1304-14
105. Kuida K, Zheng TS, Na S, Kuan C-Y, Yang D, Karasuyama H, Rakic P, Flavell RA. 1996. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384:368-72
106. Zheng TS, Hunot S, Kuida K, Flavell RA. 1999. Caspase knockouts: matters of life and death. Cell Death Differ. 6:1043-53
107. Kuida K, Haydar TF, Kuan C-Y, Gu Y, Taya C, Karasuyama H, Su MS-S, Rakic P, Flavell RA. 1998. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325-37
108. Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW. 1998. Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339-52
109. Wang S, Miura M, Jung Y-K, Zhu H, Li E, Yuan J. 1998. Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE. Cell 92:501-9
110. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J. 2000. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98-103
111. Hardy RR, Hayakawa K. 2001. B cell development pathways. Annu. Rev. Immunol. 19:595-621
112. Rolink AG, Schaniel C, Andersson J, Melchers F. 2001. Selection events operating at various stages in B cell development. Curr. Opin. Immunol. 13:202-7
113. Karasuyama H, Rolink A, Melchers F. 1996. Surrogate light chain in B cell development. Adv. Immunol. 63:1-41
114. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68:869-77
115. Shinkai Y, Rathbun G, Lain K-P, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM, Alt FW. 1992. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangements. Cell 68:855-67
116. Schuler W, Weiler IJ, Schuler A, Phillips RA, Rosenberg N, Mak TW, Kearney JF, Perry RP, Bosma MJ. 1986. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell 46:963-72
117. Strasser A, Harris AW, Corcoran LM, Cory S. 1994. bcl-2 expression promotes B but not T lymphoid development in scid mice. Nature 368:457-60
118. L transgene. Immunity 4:291-99
119. Tarlinton DM, Corcoran LM, Strasser A. 1997. Continued differentiation during B lymphopoiesis requires signals in addition to cell survival. Int. Immunol. 9:1481-94
120. Young F, Mizoguchi E, Bhan AK, Alt FW. 1997. Constitutive Bcl-2 expression during immunoglobulin heavy chain-promoted B cell differentiation expands novel precursor B cells. Immunity 6:23-33
121. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL. 1994. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180:1955-60
122. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SEG, Murray R. 1995. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181:1519-26
123. Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL. 1997. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89:1033-41
124. -/- mice. Cell 89:1011-19
125. Maraskovsky E, Peschon JJ, McKenna H, Teepe M, Strasser A. 1998. Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in interleukin-7 receptor-deficient mice but can enhance survival of mature B cells. Int. Immunol. 10:1367-75
126. Kondo M, Akashi K, Domen J, Sugamura K, Weissman IL. 1997. Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice. Immunity 7:155-62
127. Laâbi Y, Strasser A. 2000. Lymphocyte survival - Ignorance is BLys. Science 289:883-85
128. Laâbi Y, Egle A, Strasser A. 2001. TNF cytokine family: more BAFF-ling complexities. Curr. Biol. 11:R1013-16
129. Mackay F, Schneider P, Rennert P, Browning J. 2003. BAFF and APRIL: a tutorial on B cell survival. Annu. Rev. Immunol. 21:231-64
130. Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, Browning JL, Mackay F. 2000. BAFF mediates survival of peripheral immature B lymphocytes. J. Exp. Med. 192:1453-66
131. Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, Frew E, Scott ML. 2001. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 16:2111-14
132. Yan M, Brady JR, Chan B, Lee WP, Hsu B, Hatless S, Cancro M, Grewal IS, Dixit VM. 2001. Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B-cell deficiency. Curr. Biol. 11:1547-52
133. Grossmann M, O'Reilly LA, Gugasyan R, Strasser A, Adams JM, Gerondakis S. 2000. The anti-apoptotic activities of rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression. EMBO J. 19:6351-60
134. Lam KP, Kuhn R, Rajewsky K. 1997. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90:1073-83
135. Nemazee D. 2000. Receptor selection in B and T lymphocytes. Annu. Rev. Immunol. 18:19-51
136. Rathmell JC, Goodnow CC. 1994. Effects of the lpr mutation on elimination and inactivation of self-reactive B cells. J. Immunol. 153:2831-42
137. Rubio CF, Kench J, Russell DM, Yawger R, Nemazee D. 1996. Analysis of central B cell tolerance in autoimmune-prone MRL/lpr mice beating autoantibody transgenes. J. Immunol. 157:65-71
138. L escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity 9:35-45
139. Nisitani S, Tsubata T, Murakami M, Okamoto M, Honjo T. 1993. The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the periphery but not in the bone marrow. J. Exp. Med. 178:1247-54
140. Hartley SB, Cooke MP, Fulcher DA, Harris AW, Cory S, Basten A, Goodnow CC. 1993. Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death. Cell 72:325-35
141. Lang J, Arnold B, Hammerling G, Harris AW, Korsmeyer S, Russell D, Strasser A, Nemazee D. 1997. Enforced Bcl-2 expression inhibits antigen-mediated clonal elimination of peripheral B cells in an antigen dose-dependent manner and promotes receptor editing in autoreactive, immature B cells. J. Exp. Med. 186:1513-22
142. Fulcher DA, Basten A. 1994. Reduced life span of anergic self-reactive B cells in a double-transgenic model. J. Exp. Med. 179:125-34
143. + T cells. Nature 376:181-84
144. Tiegs SL, Russell DM, Nemazee D. 1993. Receptor editing in self-reactive bone marrow B cells. J. Exp. Med. 177:1009-20
145. Retter MW, Nemazee D. 1998. Receptor editing occurs frequently during normal B cell development. J. Exp. Med. 188:1231-38
146. Kurosaki T. 1999. Genetic analysis of B cell antigen receptor signaling. Annu. Rev. Immunol. 17:555-92
147. Melamed D, Benschop RJ, Cambier JC, Nemazee D. 1998. Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection. Cell 92:173-82
148. van Kooten C, Banchereau J. 1997. Functions of CD40 on B cells, dendritic cells and other cells. Curr. Opin. Immunol. 9:330-37
149. Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM. 1999. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 285:260-63
150. Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer J-L, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. 1999. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J. Exp. Med. 189:1747-56
151. Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer J-L, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J. 1998. APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J. Exp. Med. 188:1185-90
152. Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A. 2000. Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI. Curr. Biol. 10:785-88
153. Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM. 2000. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat. Immunol. 1:37-41
154. Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C. 2001. BAFF-R, a novel TNF receptor that specifically interacts with BAFF. Science 293:2108-11
155. Berberich I, Shu GL, Clark EA. 1994. Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. J. Immunol. 153:4357-66
156. Do RK, Hatada E, Lee H, Tourigny MR, Hilbert D, Chen-Kiang S. 2000. Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. J. Exp. Med. 192:953-64
157. Kuss AW, Knödel M, Berberich-Siebelt F, Lindemann D, Schimpl A, Berberich I. 1999. A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death. Eur. J. Immunol. 29:3077-88
158. Rothstein TL, Wang JKM, Panka DJ, Foote LC, Wang Z, Stanger B, Cui H, Ju S-T, Marshak-Rothstein A. 1995. Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells. Nature 374:163-65
159. Wang J, Lobito AA, Shen F, Hornung F, Winoto A, Lenardo MJ. 2000. Inhibition of fas-mediated apoptosis by the B cell antigen receptor through c-FLIP. Eur. J. Immunol. 30:155-63
160. Lam KP, Rajewsky K. 1998. Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo. Proc. Natl. Acad. Sci. USA 95:13171-75
161. Tarlinton D. 1998. Germinal centers: form and function. Curr. Opin. Immunol. 10:245-51
162. Smith KGC, Weiss U, Rajewsky K, Nossal GJV, Tarlinton DM. 1994. BCL-2 increases memory B cell recruitment but does not perturb selection in germinal centers. Immunity 1:808-13
163. Smith KGC, Light A, Nossal GJV, Tarlinton DM. 1997. The extent of affinity maturation differs between the memory and antibody-forming cell compartments in the primary immune response. EMBO J. 16:2996-3006
164. Smith KGC, Light A, O'Reilly L, Ang S-M, Strasser A, Tarlinton D. 2000. bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody forming cells. J. Exp. Med. 191:475-84
165. L transgenic mice. J. Exp. Med. 190:399-410
166. Smith KGC, Nossal GJV, Tarlinton DM. 1995. FAS is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen. Proc. Natl. Acad. Sci. USA 92:11628-32
167. + Pro-T thymocytes. Proc. Natl. Acad. Sci. USA 95:12522-27
168. Groettrup M, von Boehmer H. 1993. A role for a pre-T-cell receptor in T-cell development. Immunol. Today 14:610-14
169. Habu S, Kimura M, Katsuki M, Hioki K, Nomura T. 1987. Correlation of T cell receptor gene rearrangements to T cell surface antigen expression and to serum immunoglobulin level in scid mice. Eur. J. Immunol. 17:1467-71
170. Mombaerts P, Clark AR, Rudnicki MA, Iacomini J, Itohara S, Lafaille JJ, Wang L, Ichikawa Y, Jaenisch R, Hooper ML, Tonegawa S. 1992. Mutations in T-cell antigen receptor genes a and β block thymocyte development at different stages. Nature 360:225-31
171. Shores EW, Sharrow SO, Uppenkamp I, Singer A. 1990. T cell receptor-negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway. Eur. J. Immunol. 20:69-77
172. Malissen M, Gillet A, Ardouin L, Bouvier G, Trucy J, Ferrier P, Vivier E, Malissen B. 1995. Altered T cell development in mice with a targeted mutation of the CD3-e gene. EMBO J. 14:4641-53
173. Maraskovsky E, Teepe M, Morrissey PJ, Braddy S, Miller RE, Luynch DH, Peschon JJ. 1996. Impaired survival and proliferation in IL-7 receptor-deficient peripheral T cells. J. Immunol. 157:5315-23
174. Bogue MA, Zhu C, Aguilar-Cordova E, Donehower LA, Roth DB. 1996. p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes Dev. 10:553-65
175. Guidos CJ, Williams CJ, Grandal I, Knowles G, Huang MTF, Danska JS. 1996. V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors. Genes Dev. 10:2038-54
176. + stage of thymocyte differentiation in the absence of T cell receptor rearrangement. J. Exp. Med. 183:1923-28
177. Kabra NH, Kang C, Hsing LC, Zhang J, Winoto A. 2001. T cell-specific FADD-deficient mice: FADD is required for early T cell development. Proc. Natl. Acad. Sci. USA 98:6307-12
178. Newton K, Harris AW, Strasser A. 2000. FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor. EMBO J. 19:931-41
179. Nishimura Y, Ishii A, Kobayashi Y, Yamasaki Y, Yonehara S. 1995. Expression and function of mouse Fas antigen on immature and mature T cells. J. Immunol. 154:4395-403
180. + thymocytes by the anti-Fas antibody. J. Exp. Med. 181:485-91
181. Petrie HT, Livak F, Schatz DG, Strasser A, Crispe NI, Shortman K. 1993. Multiple rearangements in TCR-a chain genes maximize the production of useful thymocytes. J. Exp. Med. 178:615-22
182. Sebzda E, Mariathasan S, Ohteki T, Jones R, Bachmann MF, Ohashi PS. 1999. Selection of the T cell repertoire. Annu. Rev. Immunol. 17:829-74
183. + thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alphainstability, improves TCR assembly, and parallels other indicators of positive selection. J. Exp. Med. 181:193-202
184. Turka LA, Schatz DG, Oettinger MA, Chun JJM, Gorka C, Lee K, McCormack WT, Thompson CB. 1991. Thymocyte expression of RAG-1 and RAG-2: termination by T cell receptor cross-linking. Science 253:778-81
185. + thymocytes in vitro induces early aspects of positive selection, but not apoptosis. J. Immunol. 158:65-75
186. Strasser A, Hams AW, von Boehmer H, Cory S. 1994. Positive and negative selection of T cells in T cell receptor transgenic mice expressing a bcl-2 transgene. Proc. Natl. Acad. Sci. USA 91:1376-80
187. + stage during positive selection and promotes thymocyte differentiation at several control points. Immunity 1:197-205
188. Calnan BJ, Szychowski S, Chan FK, Cado D, Winoto A. 1995. A role for the orphan steroid receptor Nut77 in apoptosis accompanying antigen-induced negative selection. Immunity 3:273-82
189. Zhou T, Cheng J, Yang P, Wang Z, Liu C, Su X, Bluethmann H, Mountz JD. 1996. Inhibition of Nur77/Nurr1 leads to inefficient clonal deletion of self-reactive T cells. J. Exp. Med. 183:1879-92
190. Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, Tsubata T, Ohashi PS, Koyasu S, Penninger JM, Nakano T, Mak TW. 2001. T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14:523-34
191. L levels in vivo. J. Exp. Med. 191:1721-34
192. Teague TK, Marrack P, Kappler JW, Vella AT. 1997. IL-6 rescues resting mouse T cells from apoptosis. J. Immunol. 158:5791-96
193. Vella A, Teague TK, Ihle J, Kappler J, Marrack P. 1997. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: Stat6 is probably not required for the effect of IL-4. J. Exp. Med. 186:325-30
194. Kirberg J, Berns A, von Boehmer H. 1997. Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules. J. Exp. Med. 186:1269-75
195. + T cells, but affect their long-term life span. Immunity 5:217-28
196. Tanchot C, Lemonnier FA, Péramau B, Freitas AA, Rocha B. 1997. Differential requirements for survival and proliferation of CD8 naive or memory T cells. Science 276:2057-62
197. + T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. J. Exp. Med. 191:355-64
198. Vella AT, Dow S, Potter TA, Kappler J, Marrack P. 1998. Cytokine-induced survival of activated T cells in vitro and in vivo. Proc. Natl. Acad. Sci. USA 95:3810-15
199. Duke RC, Cohen JJ. 1986. IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res. 5:289-99
200. Suzuki H, Kundig TM, Furlonger C, Wakeham A, Timms E, Matsuyama T, Schmits R, Simard JJ, Ohashi PS, Griesser H, Taniguchi T, Paige CJ, Mak TW. 1995. Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science 268:1472-76
201. Schorle H, Holtschke T, Hunig T, Schimpl A, Horak I. 1991. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352:621-24
202. Li XC, Demirci G, Ferrari-Lacraz S, Groves C, Coyle A, Malek TR, Strom TB. 2001. IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat. Med. 7:114-18
203. Russell JH, Rush B, Weaver C, Wang R. 1993. Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. Proc. Natl. Acad. Sci. USA 90:4409-13
204. Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH. 1995. Fas ligand mediates activation-induced cell death in human T lymphocytes. J. Exp. Med. 181:71-77
205. Brunner T, Mogil RJ, LaFace D, Yoo NJ, Mahboubi A, Echeverri F, Martin SJ, Force WR, Lynch DH, Ware CF, Green DR. 1995. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373:441-44
206. Dhein J, Walczak H, Baumler C, Debatin K-M, Krammer PH. 1995. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 373:438-41
207. Ju S-T, Panka DJ, Cui H, Ettinger R, El-Khatib M, Sherr DH, Stanger BZ, Marshak-Rothstein A. 1995. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373:444-48
208. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schröter M, Burns K, Mattmann C, Rimoldi D, Tschopp J. 1997. Inhibition of death receptor signals by cellular FLIP. Nature 388:190-94
209. Suda T, Tanaka M, Miwa K, Nagata S. 1996. Apoptosis of mouse naive T cells induced by recombinant soluble Fas ligand and activation-induced resistance to Fas ligand. J. Immunol. 157:3918-24
210. Refaeli Y, Van Parijs L, London CA, Tschopp J, Abbas AK. 1998. Biochemical mechanisms of IL-2-regulated Fasmediated T cell apoptosis. Immunity 8:615-23
211. Metcalf D. 1997. The molecular control of granulocytes and macrophages. Ciba Found. Symp. 204:40-50
212. Mollinedo F, Borregaard N, Boxer LA. 1999. Novel trends in neutrophil structure, function and development. Immunol. Today 20:535-37
213. Chuang PI, Yee E, Karsan A, Winn RK, Harlan JM. 1998. A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils. Biochem. Biophys. Res. Commun. 249:361-65
214. Epling-Burnette PK, Zhong B, Bai F, Jiang K, Bailey RD, Garcia R, Jove R, Djeu JY, Loughran TP Jr, Wei S. 2001. Cooperative regulation of Mcl-1 by Janus kinase/STAT and phosphatidylinositol 3-kinase contribute to Granulocyte-Macrophage Colony-Stimulating Factor-delayed apoptosis in human neutrophils. J. Immunol. 166:7486-95
215. Moulding DA, Quayle JA, Hart CA, Edwards SW. 1998. Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 92:2495-502
216. Hamasaki A, Sendo F, Nakayama K, Ishida N, Negishi I, Nakayama K-I, Hatakeyama S. 1998. Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene. J. Exp. Med. 188:1985-92
217. Fecho K, Bentley SA, Cohen PL. 1998. Mice deficient in fas ligand (gld) or fas (lpr) show few alterations in granulopoiesis. Cell Immunol. 188:19-32
218. Traver D, Akashi K, Weissman IL, Lagasse E. 1998. Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia. Immunity 9:47-57
219. Bochner BS, Schleimer RP. 2001. Mast cells, basophils, and eosinophils: distinct but overlapping pathways for recruitment. Immunol. Rev. 179:5-15
220. Xiang Z, Ahmed AA, Moller C, Nakayama K, Hatakeyama S, Nilsson G. 2001. Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. J. Exp. Med. 194:1561-69
221. Orlofsky A, Somogyi RD, Weiss LM, Prystowsky MB. 1999. The murine antiapoptotic protein A1 is induced in inflammatory macrophages and constitutively expressed in neutrophils. J. Immunol. 163:412-19
222. + lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway. Proc. Natl. Acad. Sci. USA 92:11225-29
223. Dang-Vu AP, Pisetsky DS, Weinberg JB. 1987. Functional alterations of macrophages in autoimmune MRL-lpr/lpr mice. J. Immunol. 138:1757-61
224. Perlman H, Pagliari LJ, Georganas C, Mano T, Walsh K, Pope RM. 1999. FLICE-inhibitory protein expression during macrophage differentiation confers resistance to fas-mediated apoptosis. J. Exp. Med. 190:1679-88
225. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767-811
226. Sparwasser T, Vabulas RM, Villmow B, Lipford GB, Wagner H. 2000. Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins. Eur. J. Immunol. 30:3591-97
227. Wong BR, Josien R, Lee SY, Sauter B, Li H-L, Steinman RM, Choi YW. 1997. TRANCE (Tumor Necrosis Factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J. Exp. Med. 186:2075-80
228. Björck P, Banchereau J, Flores-Romo L. 1997. CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells. Int. Immunol. 9:365-72
229. Park Y, Lee SW, Sung YC. 2002. Cutting edge: CpG DNA inhibits dendritic cell apoptosis by up-regulating cellular inhibitor of apoptosis proteins through the phosphatidylinositide-3′-OH kinase pathway. J. Immunol. 168:5-8
230. Ashany D, Savir A, Bhardwaj N, Elkon KB. 1999. Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway. J. Immunol. 163:5303-11
231. Rieux-Laucat F, Le Deist F, Hivroz C, Roberts LAG, Debatin KM, Fischer A, de Villartay JP. 1995. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268:1347-49
232. Cohen PL, Eisenberg RA. 1991. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol. 9:243-69
233. Tsujimoto Y, Croce CM. 1986. Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc. Natl. Acad. Sci. USA 83:5214-18
234. Strasser A, Harris AW, Cory S. 1993. Em-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. Oncogene 8:1-9
235. Strasser A, Harris AW, Bath ML, Cory S. 1990. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between mycand bcl-2. Nature 348:331-33
236. Acton D, Domen J, Jacobs H, Vlaar M, Korsmeyer S, Betas A. 1992. Collaboration of PIM-1 and BCL-2 in lymphomagenesis. Curr. Top. Microbiol. Immunol. 182:293-98
237. Kogan SC, Brown DE, Shultz DB, Truong BT, Lallemand-Breitenbach V, Guillemin MC, Lagasse E, Weissman IL, Bishop JM. 2001. BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor a chimeric protein (PML-RARa) to block neutrophil differentiation and initiate acute leukemia. J. Exp. Med. 193:531-43
238. Nieborowska-Skorska M, Hoser G, Kossev P, Wasik MA, Skorski T 2002. Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Blood 99:4531-39
239. Tamiya S, Etoh K, Suzushima H, Takatsuki K, Matsuoka M. 1998. Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells. Blood 91:3935-42
240. Beltinger C, Kurz E, Böhler T, Schrappe M, Ludwig WD, Debatin KM. 1998. CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia. Blood 91:3943-51
241. Peng SL, Robert ME, Hayday AC, Craft J. 1996. A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice. J. Exp. Med. 184:1149-54
242. Davidson WF, Giese T, Fredrickson TN. 1998. Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions. J. Exp. Med. 187:1825-38
243. Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A. 1993. Epstein virus-coded BHRF 1 protein, a viral homologue of Bcl-2 protects human B cells from programmed cell death. Proc. Natl. Acad. Sci. USA 90:8479-83
244. Cheng EH-Y, Nicholas J, Bellows DS, Hayward GS, Guo H-G, Reitz MS, Hardwick JM. 1997. A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc. Natl. Acad. Sci. USA 94:690-94
245. Sarid R, Sato T, Bohenzky RA, Russo JJ, Chang Y. 1997. Kaposi's sarcomaassociated herpesvirus encodes a functional Bcl-2 homologue. Nat. Med. 3:293-98
246. Said W, Chien K, Takeuchi S, Tasaka T, Asou H, Cho SK, de Vos S, Cesarman E, Knowles DM, Koeffler HP. 1996. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) in primary effusion lymphoma: ultrastructural demonstration of herpesvims in lymphoma cells. Blood 87:4937-43
247. Zauli G, Gibellini D, Caputo A, Bassini A, Negrini M, Monne M, Mazzoni M, Capitani S. 1995. The human immunodeficiency virus type-1 Tatprotein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Blood 86:3823-34
248. Sturzl M, Hohenadl C, Zietz C, Castanos-Velez E, Wunderlich A, Ascherl G, Biberfeld P, Monini P, Browning PJ, Ensoli B. 1999. Expression of K13/v-FLIP gene of human herpesvirus 8 and apoptosis in Kaposi's sarcoma spindle cells. J. Natl. Cancer Inst. 91:1725-33
249. Tepper CG, Seldin MF. 1999. Modulation of caspase-8 and FLICE-inhibitory protein expression as a potential mechanism of Epstein-Barr virus tumori-genesis in Burkitt's lymphoma. Blood 94:1727-37
250. Wang SD, Huang KJ, Lin YS, Lei HY. 1994. Sepsis-induced apoptosis of the thymocytes in mice. J. Immunol. 152:5014-21
251. + T lymphocytes in humans. J. Immunol. 166:6952-63
252. Hotchkiss RS, Swanson PE, Knudson CM, Chang KC, Cobb JP, Osborne DF, Zollner KM, Buchman TG, Korsmeyer SJ, Karl IE. 1999. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J. Immunol. 162:4148-56
253. Hotchkiss RS, Tinsley KW, Swanson PE, Chang KC, Cobb JP, Buchman TG, Korsmeyer SJ, Karl IE. 1999. Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc. Natl. Acad. Sci. USA 96:14541-56
254. Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P, Xanthoudakis S, Roy S, Black C, Grimm E, Aspiotis R, Han Y, Nicholson DW, Karl IE. 2000. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat. Immunol. 1:496-501
255. Lassus P, Opitz-Araya X, Lazebnik Y. 2002. Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 297:1352-54
256. Marsden VS, O'Connor L, O'Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A. 2002. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature 419:634-37
257. Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM. 2002. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-κB2. Immunity 17:515-24