Signals and susceptibility to programmed death in B cells

Current Opinion in Immunology

Volumn 8, Issue 3, 1996, Pages 362-371

  Rothstein, Thomas L ^a  

^a BOSTON MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD40 ANTIGEN; COMPLEMENT COMPONENT C3D RECEPTOR; FAS ANTIGEN; INTERLEUKIN 4 RECEPTOR; SECRETORY IMMUNOGLOBULIN;

APOPTOSIS; B LYMPHOCYTE; IMMUNOREGULATION; REVIEW;

EID: 0030175708     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(96)80126-9     Document Type: Article

References (133)

1. Ashwell J. Lymphocyte programmed cell death. Snow EC. Handbook of B and T Lymphocytes. 1994;63-89 Academic Press, San Diego.
2. Rothstein TL, Wang JKM, Panka DJ, Foote LC, Wang Z, Stanger B, Cui H, Ju S-T, Marshak-Rothstein A. Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells. of outstanding interest Nature. 374:1995;163-166 Engagement of CD40 on primary B cells by CD40L stimulates Fas expression and induces exquisite sensitivity to Fas-mediated apoptosis. In contrast, B cells stimulated by the combination of anti-IgM (or specific antigen) plus CD40L upregulate Fas expression, but are resistant to Fas-induced cell death. Thus, sIgM triggering produces an inducible state of Fas-resistance.
3. Garrone P, Neidhardt EM, Garcia E, Galibert L, Van Kooten C, Banchereau J. Fas ligation induces apoptosis of CD40 activated human B lymphocytes. of special interest J Exp Med. 182:1995;1265-1273 Engagement of CD40 on human tonsillar B cells by CD40L or CD40-specific antibody stimulates expression of Fas and induces sensitivity to FAS-mediated apoptosis; thus, CD40 signaling is associated with enhanced susceptibility to cell death, as shown in [4] also.
4. Schattner EJ, Elkon KB, Yoo D-Y, Tumang J, Krammer PH, Crow MK, Friedman SM. CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway. J Exp Med. 182:1995;1557-1565 Engagement of CD40 on human tonsillar B cells by CD40 ligand, CD40-specific antibody, or T cells stimulates Fas expression and induces sensitivity to Fas-mediated apoptosis; thus, CD40 signaling is associated with enhanced susceptibility to cell death. See annotation [3].
5. of special interest Cambier JC, Pleiman CM, Clark MR. Signal transduction by the B cell antigen receptor and its coreceptors. Annu Rev Immunol. 12:1994;457-486.
6. Banchereau J, Bazan F, Blanchard D, Brière F, Galizzi JP, Van Kooten C, Liu YJ, Rousset F, Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 12:1994;881-922.
7. Keegan AD, Nelms K, Wang L-M, Pierce JH, Paul WE. Interleukin 4 receptor: signaling mechanisms. Immunol Today. 15:1994;423-432.
8. Fearon DT, Carter RH. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu Rev Immunol. 13:1995;127-149.
9. Norvell A, Mandik L, Monroe JG. Engagement of the antigen-receptor on immature murine B lymphocytes results in death by apoptosis. of special interest J Immunol. 154:1995;4404-4413 The inhibitory effect of sIgM engagement on primary, immature B cells (derived from murine bone marrow and neontal spleen) is shown conclusively to result from apoptotic deletion. Protein synthesis is necessary for this process, and IL-4 reverses apoptotic signaling.
10. Parry SL, Holman MJ, Hasbold J, Klaus GGB. Plastic-immobilized anti-μ or anti-δ antibodies induce apoptosis in mature murine B lymphocytes. Eur J Immunol. 24:1994;974-979.
11. Parry SL, Hasbold J, Holman M, Klaus GGB. Hypercross-linking surface IgM or IgD receptors on mature B cells induces apoptosis that is reversed by costimulation with IL-4 and anti-CD40. of special interest J Immunol. 152:1994;2821-2829 Hypercross-linking of slg on mature B cells, beyond that typically used to trigger cell-cycle progression, leads to apoptosis that is reversed by T cell products. This suggests that mature, recirculating B cells may yet be subject to tolerance induction through antigen-receptor interactions, subject to modulation by T cells. See also [10].
12. Valentine MA, Licciardi KA. Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40. Eur J Immunol. 22:1992;3141-3148.
13. Tsubata T, Wu J, Honjo T. B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature. 364:1993;645-648.
14. L induction.
15. L induction participates in opposing apoptosis in this model.
16. L coupling as an explanation for the anti-apoptotic effect of CD40 engagement in all WEHI-231 sublines.
17. L Cdk4, and Cdk6. Implication of their cooperation in selective B cell growth. of special interest J Immunol. 155:1995;5527-5535 CD40 engagement of CD40 by CD40-specific antibody rescues WEHI-231 B cells from sIgM-mediated apoptosis and induces bcl-x gene expression, whereas anti-IgM reduces expressed bcl-x. Overexpression of bcl-x inhibits sIgM-induced cell death, but does not foster cell-cycle progression as anti-CD40 does, suggesting that bcl-x is one of several downstream mediators triggered by CD40 that promotes B cell viability.
18. Scott DW, O'Garra A, Warren D, Klaus GGB. Lymphoma models for B cell activation and tolerance. VI. Reversal of anti-Ig-mediated negative signaling by T cell-derived lymphokines. J Immunol. 139:1987;3924-3929.
19. Komada Y, Zhang XL, Zhou YW, Tanaka S, Higashigawa M, Ido M, Sakurai M. Apoptotic cell death induced by anti-IgM antibody and phorbol esters is inhibited by interleukin-4 in human B lymphoma cell line MBC-1. Cell Immunol. 159:1994;279-283.
20. Igarashi H, Kuwahara K, Nomura J, Matsuda A, Kikuchi K, Inui S, Sakaguchi N. B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell and mature B cell. J Immunol. 153:1994;2381-2393.
21. Gottschalk AR, McShan CL, Kilkus J, Dawson G, Quintana J. Resistance to anti-IgM-induced apoptosis in a WEHI-231 subline is due to insufficient production of ceramide. of special interest Eur J Immunol. 25:1995;1032-1038 Resistance to sIgM-mediated apoptosis in one WEHI-231 subline is traced to deficient generation of ceramide, among many sIgM-triggered events studied. See also [71,72,73] regarding the role of sphingomyelinase and ceramide in apoptosis.
22. Fukuda T, Kitamura D, Taniuchi I, Maekawa Y, Benhamou LE, Sarthou P, Watanabe T. Restoration of surface IgM-mediated apoptosis in an anti-IgM-resistant variant of WEHI-231 lymphoma cells by HS1, a protein-tyrosine kinase substrate. Proc Natl Acad Sci USA. 92:1995;7302-7306.
23. Kozono Y, Duke RC, Schleicher MS, Holers VM. Co-ligation of mouse complement receptors 1 and 2 with surface IgM rescues splenic B cells and WEHI-231 cells from anti-surface IgM-induced apoptosis. of special interest Eur J Immunol. 25:1995;1013-1017 Co-cross-linking complement receptors 1 and 2 with the antigen receptor partially reverses apoptosis induced by anti-IgM alone in WEHI-231 and primary murine B cells, although all anti-CR antibodies are not equally effective. This work demonstrates that costimulatory complement receptors may influence apoptosis induced by sIgM.
24. Chaouchi N, Vazquez A, Galanaud P, Leprince C. B cell antigen receptor-mediated apoptosis. Importance of accessory molecules CD19 and CD22, and of surface IgM cross-linking. of special interest J Immunol. 154:1995;3096-3104 In Ramos and primary human B cells, cross-linking of CD19 induces apoptosis, and apoptosis induced by anti-IgM is enhanced by co-cross-linking of CD19 with the antigen receptor. Because intracellular signaling produced by CD21 is thought to be transmitted via CD19, these results differ from those in [23], although they again indicate that co-receptors may influence apoptotic signaling produced by sIgM.
25. L protects WEHI-231 B cells from sIgM-induced apoptosis, as well as apoptosis induced by ceramide. With respect to cell death mediated by anti-IgM, these results parallel those reported in [14,16,17].
26. Cuende E, Ales-Martinez JE, Ding L, Gonzalez-Garcia M, Martinez C, Nuñez G. Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells. EMBO J. 12:1993;1555-1560.
27. Holder MJ, Wang H, Milner AE, Casamayor M, Armitage R, Spriggs MK, Fanslow WC, MacLennan ICM, Gregory CD, Gordon J. Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bcl-2 induction. Eur J Immunol. 23:1993;2368-2371.
28. Chen M, Quintans J, Fuks Z, Thompson C, Kufe DW, Weichselbaum RR. Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide. Cancer Res. 55:1995;991-994.
29. Sama V, Lin Z, Clark L, Rust BM, Tewari M, Noelle RJ, Dixit VM. Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis. J Biol Chem. 270:1995;12343-12346.
30. Fischer G, Kent SC, Joseph L, Green DR, Scott DW. Lymphoma models for B cell activation and tolerance. X. Anti-M-mediated growth arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization of myc. of outstanding interest J Exp Med. 179:1994;221-228 Apoptosis induced by anti-IgM in WEHI-231 and CH31 B cells is inhibited by antisense directed against c-myc. Antisense stabilizes c-myc, such that the typical anti-IgM-induced decline in the levels of mRNA and protein do not occur. These results suggest that the late decline in c-myc is responsible for sIgM-mediated apoptosis, rather than the early increase.
31. Lee H, Arsura M, Wu M, Duyao M, Buckler AJ, Sonenshein GE. Role of Rel-related factors in control of c-myc gene transcription in receptor-mediated apoptosis of the murine B cell WEHI 231 line. of outstanding interest J Exp Med. 181:1995;1169-1177 Changes in Rel-related factors regulate c-myc expression in WEHI-231 B cells following sIgM engagement, the levels of which have been implicated in specifying cell death (see [30]). These results suggest that expression of NF-κB may play a role in antigen-receptor mediated apoptosis, and in turn focus attention on coupling between sIgM and lκB. See also [76], which suggests that Bcl-2 may affect levels of NF-κB.
32. of special interest Daniel PT, Krammer PH. Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J Immunol. 152:1994;5624-5632.
33. + cytotoxic T cells. Proc Natl Acad Sci USA. 91:1994;4185-4189.
34. Rothstein TL, Foote LC, Schneider TJ, Fischer GM, Jacobson BA, Lynch DH, Ju S-T, Marshak-Rothstein A. Inducible resistance to Fas-mediated apoptosis in primary B lymphocytes. Adv Exp Med Biol. 1996;. in press.
35. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S-I, Sameshima M, Hase A, Seto Y, Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 66:1991;233-243.
36. Tewari M, Dixit VM. Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J Biol Chem. 270:1995;3255-3260.
37. Ramsdell F, Seaman MS, Miller RE, Picha KS, Kennedy MK, Lynch DH. Differential ability of Th1 and Th2 cells to express Fas ligand and to undergo activation-induced cell death. of special interest Int Immunol. 6:1994;1545-1553 Long term Th1 but not Th2 cell lines can be induced to express relatively high levels of FasL, providing another distinction between T cell subpopulations and the potential for nonreciprocal interactions.
38. Yoshino T, Kondo E, Cao L, Takahashi K, Hayashi K, Nomura S, Akagi T. Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes. Blood. 83:1994;1856-1861.
39. Smith KGC, Nossal GJV, Tarlinton DM. Fas is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen. of outstanding interest Proc Natl Acad Sci USA. 92:1995;11628-11632 Although Fas expression is normally elevated on germinal center B cells, the responses of Fas-deficient B6//pr and B6/+ mice are essentially comparable following immunization with a hapten-protein conjugate with regard to the generation of antibody forming cells, memory B cells, and affinity maturation of the induced repertoire. Thus, Fas appears to be irrelevant to B cell selection in germinal centers.
40. Jacobson BA, Panka DJ, Nguyen K-A, Erikson J, Abbas AK, Marshak-Rothstein A. Anatomy of autoantibody production: dominant localization of antibody-producing cells to T cell zones in Fas-deficient mice. of outstanding interest Immunity. 3:1995;509-519 In Fas-deficient mice, B cells producing autoantibody are found initially in the T-cell rich inner PALS of the spleen, not in germinal centers, indicating that the inner PALS is normally an important site for the Fas-dependent regulation of autoreactive B cells.
41. + T cells capable of producing Fas ligand, suggesting that Fas dependent mechanisms control the deletion of anergic, autoreactive B cells.
42. Cleary AM, Fortune SM, Yellin MJ, Chess L, Lederman S. Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J Immunol. 155:1995;3329-3337.
43. Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan ICM. Mechanism of antigen-driven selection in germinal centres. Nature. 342:1989;929-931.
44. Mangeney M, Richard Y, Coulaud D, Tursz T, Wiels J. CD77: an antigen of germinal center B cells entering apoptosis. Eur J Immunol. 21:1991;1131-1140.
45. Lindhout E, Lakeman A, De Groot C. Follicular dendritic cells inhibit apoptosis in human B lymphocytes by a rapid and irreversible blockade of preexisting endonuclease. J Exp Med. 181:1985;1985-1995.
46. Bonnefoy JY, Henchoz S, Hardie D, Holder MJ, Gordon J. A subset of anti-CD21 antibodies promote the rescue of germinal center B cells from apoptosis. Eur J Immunol. 23:1993;969-972.
47. Zupo S, Rugari E, Dono M, Taborelli G, Malavasi F, Ferrarini M. CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells. Eur J Immunol. 24:1994;1218-1222.
48. Levy Y, Brouet J-C. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest. 93:1994;424-428.
49. Holder M, Grafton G, MacDonald I, Finney M, Gordon J. Engagement of CD20 suppresses apoptosis in germinal center B cells. Eur J Immunol. 25:1995;3160-3164.
50. Koopman G, Keehnen RM, Lindhout E, Newman W, Shimizu Y, Van Seventer GA, De Groot C, Pals ST. Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and VLA-4 (CD49d)-VCAM-1(CD106) pathways prevents apoptosis of germinal center B cells. J Immunol. 152:1994;3760-3767.
51. Pulendran B, Kannourakis G, Nourl S, Smith KGC, Nossal GJV. Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. of special interest Nature. 375:1995;331-334 A model system consisting of soluble, deaggregated antigen administered to immunized mice demonstrates that germinal center B cells encountering 'autologous' antigen are rapidly eliminated by apoptosis in situ. Thus, the nature of sIgM engagement may dictate the subsequent fate of B cells.
52. Liu YJ, Mason DY, Johnson GD, Abbott S, Gregory CD, Hardie DL, Gordon J, MacLennan ICM. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol. 21:1991;1905-1910.
53. Hu HM, O'Rourke K, Boguski MS, Dixit VM. A novel RING finger protein interacts with the cytoplasmic domain of CD40. of special interest J Biol Chem. 269:1994;30069-30072 A novel zinc ring/zinc finger-containing protein ('CD40bp') is identified on the basis of interaction with the cytoplasmic tail of CD40 in a yeast two-hybrid screen and is shown to be expressed in B cell lines. CD40bp is noted to be homologous to TRAF2 and is presently termed 'TRAF3'.
54. Cheng G, Cleary AM, Ye Z-S, Hong DI, Lederman S, Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. of special interest Science. 267:1995;1494-1498 A novel zinc ring/zinc finger-containing protein ('CRAF1') is identified on the basis of interaction with the cytoplasmic tail of CD40 in a yeast two-hybrid screen. CRAF1 is noted to be homologous to TRAF 1 and 2 in the carboxy-terminal region and is presently termed 'TRAF3'. A deletion of TRAF3 that acts as a dominant-negative mutant inhibits CD40 mediated induction of CD23 and, thus, TRAF3 appears to be functional.
55. Sato T, Irie S, Reed JC. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. of special interest FEBS Letters. 358:1995;113-118 A novel zinc ring/zinc finger-containing protein ('CAP-1') is identified on the basis of interaction with the cytoplasmic tail of CD40 in a yeast two-hybrid screen. CAP-1 is noted to be homologous to TRAF 1 and 2 in the carboxy-terminal region. It is slightly smaller than CD40bp/CRAF-1/TRAF-3 and may represent a splice variant.
56. Rothe M, Sarma V, Dixit VM, Goeddel DV. TRAF2-mediated activation of NF-κB by TNF receptor 2 and CD40. of outstanding interest Science. 269:1995;1424-1426 Yeast two-hybrid analysis shows that TRAF2 binds CD40 as well as TNF-R2. Overexpression of TRAF2 (but not TRAF3 or TRAF1) induces NF-κB and κB-dependent reporter gene activity. Expression of a deletion mutant of TRAF2, that lacks the RING finger and acts as a dominant negative, blocks CD40 mediated induction of NF-κB, as does expression of TRAF3. Thus, TRAF2 mediates induction of NF-κB by CD40, for which TRAF3 is inhibitory. Along with [54], this suggests that distinct CD40-binding proteins direct separate signaling pathways leading to NF-κB and CD23.
57. Wortis HH, Teutsch M, Higer M, Zheng J, Parker DC. B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes. of special interest Proc Natl Acad Sci USA. 92:1995;3348-3352 Both anti-IgM and CD40L stimulate B cell activation and proliferation, but different intracellular signaling pathways are utilized, as demonstrated by the differential effects of metabolic inhibitors, and distinct phenotypic outcomes are also observed.
58. Marshall LS, Shepherd DM, Ledbetter JA, Aruffo A, Noelle RJ. Signaling events during helper T cell-dependent B cell activation. I. Analysis of the signal transduction pathways triggered by activated helper T cell in resting B Cells. J Immunol. 152:1994;4816-4825.
59. Lalmanach-Girard A-C, Chiles TC, Parker DC, Rothstein TL. T cell-dependent induction of NF-κB in B cells. J Exp Med. 177:1993;1215-1219.
60. Huo L, Rothstein TL. Receptor-specific induction of individual AP-1 components in B lymphocytes. of special interest J Immunol. 154:1995;3300-3309 Both anti-IgM and CD40L stimulate nuclear expression of the AP-1 transcription factor complex in primary B cells. AP-1 fosljun components are comparably induced following engagement of both receptors, with the exception that fosB mRNA, and protein is not stimulated by CD40L although both are strongly induced by anti-IgM. Thus, despite overall similarity in AP-1 transcription factor induction, subtle receptor-specific differences exist in the recruitment of AP-1 components.
61. Ren CL, Morio T, Fu SM, Geha RS. Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C2. of special interest J Exp Med. 179:1994;673-680 Engagement of CD40 on human Daudi cells by antibody specific for CD40 is shown to produce phosphorylation and activation of Lyn kinase and PI-3 kinase, and phosphorylation of PLCγ2. These downstream events are reminiscent of sIgM triggering. See also [57].
62. Faris M, Gaskin F, Parsons JT, Fu SM. CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn and Syk and the appearance of a 28-kD tyrosine phosphorylated protein. J Exp Med. 179:1994;1923-1931.
63. Ivashkiv LB. Cytokines and STATs: how can signals achieve specificity? Immunity. 3:1995;1-4.
64. Tedder TF, Zhou L-J, Engel P. The CD19/CD21 signal transduction complex of B lymphocytes. Immunol Today. 15:1994;437-442.
65. Carter RH, Tuveson DA, Park DJ, Rhee SG, Fearon DT. The CD19 complex of B lymphocytes. Activation of phospholipase C by a protein tyrosine kinase-dependent pathway that can be enhanced by the membrane IgM complex. J Immunol. 147:1991;3663-3671.
66. Chalupny NJ, Aruffo A, Esselstyn JM, Chan PY, Bajorath J, Blake J, Gilliland LK, Ledbetter JA, Tepper MA. Specific binding of Fyn and phosphatidylinositol 3-kinase to the B cell surface glycoprotein CD19 through their src homology 2 domains. Eur J Immunol. 25:1995;2978-2984.
67. Luxembourg AL, Cooper NR. Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV. J Immunol. 153:1994;4448-4457.
68. Francis DA, Ke X-Y, Sen R, Rothstein TL. Induction of the transcription factors NF-κB, AP-1 and NF-AT during B cell stimulation through the CD40 receptor. of special interest Int Immunol. 7:1995;151-161 Engagement of CD40 on primary murine B cells by CD40L induces nuclear expression of NF-κB, AP-1 and NF-AT transcription factor complexes that parallels induction by anti-IgM. However anti-IgM induces NF-κB in a PKC-dependent fashion, whereas induction of NF-κB induction by CD40L is PKC-independent. These results suggest that nuclear outcomes of CD40 and sIgM triggering may be similar despite differences in intermediary signaling pathways, and question the basis for receptor-specific differences in B cell responses.
69. Berberich I, Shu GL, Clark EA. Cross-linking CD40 on B cells rapidly activates nuclear factor-κB. J Immunol. 153:1994;4357-4366.
70. Choi MSK, Brines RD, Holman MJ, Klaus GGB. Induction of NF-AT in normal B lymphocytes by anti-immunoglobulin or CD40 ligand in conjunction with IL-4. Immunity. 1:1994;179-187.
71. Cifone MG, Roncaioli P, De Maria R, Camarda G, Santoni A, Ruberti G, Testi R. Multiple pathways originate at the Fas/APO-1 (CD95) receptor: sequential involvement of phosphatidylcholine-specific phospholipase C and acidic sphingomyelinase in the propagation of the apoptotic signal. of special interest EMBO J. 14:1995;5859-5868 Updating an earlier report by this group (J Exp Med, 177: 1547-1552), the present results implicate PC-PLC and acid sphingomyelinase as direct and critical mediators of Fas-mediated apoptosis, on the basis of work with Fas-resistent and Fas-sensitive clones of HuT78. Because acid sphingomyelinase is located within lysosomes, these data imply that Fas-induced signals traverse the lysosomal membrane; thus compartmentalizing of mediators may provide an additional level of regulation for apoptotic events. See also references [72,73].
72. of outstanding interest Gulbins E, Bissonnette R, Mahboubi A, Martin S, Nishioka W, Brunner T, Baier G, Baier-Bitterlich G, Byrd C, Lang F, et al. Fas-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway. of outstanding interest Immunity. 2:1995;341-351 In studies with Jurkat and P815 cells, Fas is shown to stimulate sphingomyelinase, induce ceramide accumulation, and trigger Ras activation. Anti-Ras and dominant-negative Ras interfered with Fas-mediated apoptosis. These results support a role for ceramide and extend the Fas death pathway to include Ras. It is unclear at this time, however, whether positive downstream events typically induced following activation of Ras are triggered by Fas engagement, and if not, why not. See also [77].
73. Tepper CG, Jayadev S, Liu B, Bielawska A, Wolff R, Yonehara S, Hannun YA, Seldin MF. Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity. Proc Natl Acad Sci USA. 92:1995;8443-8447 Engagement of Fas leads to ceramide accumulation which, through study of Fas-resistant and Fas-sensitive human B cell lines, appears to play an important role in bringing about Fas-mediated apoptosis. Activation of PKC opposes Fas-induced cytotoxicity, suggesting opposing roles for ceramide and diacylglycerol lipid-derived mediators.
74. of special interest Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 348:1990;334-336.
75. Hockenbery DM, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 75:1993;241-251.
76. Ivanov VN, Deng G, Podack ER, Malek TR. Pleiotropic effects of Bcl-2 on transcription factors in T cells: potential role of NF-κB p50-p50 for the anti-apoptotic function of Bcl-2. Int Immunol. 7:1995;1709-1720 Transfection of 2B4 T cells with bcl-2 results in baseline changes in the levels of several transcription factors, notably NF-κB. Additional changes occur following apoptotic stimuli. This provocative report raises the possibility that Bcl-2 family members act in part by altering transcriptional regulation.
77. Ras in Ras-induced apoptosis. J Biol Chem. 271:1996;1-5.
78. Rothe M, Pan M-G, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. of outstanding interest Cell. 83:1995;1243-1252 Two TRAF2-interacting proteins are identified and cloned and found to be homologous to baculovirus inhibitor of apoptosis proteins (c-IAP1, c-IAP2). Each contains three baculoviral inhibition of apoptosis protein repeat (BIR) sequences. Overexpression of these proteins did not suppress apoptosis induced by Fas or TNF engagement, but related results [79] suggest that this family may regulate cell death.
79. of special interest Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton-Horvat G, Farahani R, McLean M, Ikeda J-E, MacKenzie A, Korneluk RG. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. of special interest Nature. 379:1996;349-353 Three human genes homologous to baculovirus inhibitor of apoptosis proteins and neuronal apoptosis inhibitor protein are identified (xiap, hiap-1, hiap-2). Each contains three baculoviral inhibition of apoptosis protein repeat (BIR) sequences. Expression of each produces an anti-apoptotic effect. These results define a new family of mammalian apoptosis inhibitors, and on the basis of related work [78] these inhibitors may interact with TRAF proteins.
80. of special interest Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. of special interest Science. 263:1994;1759-1762 A variant form of Fas lacking the transmembrane region is identified in RNA from normal and diseased individuals. This soluble form of Fas inhibits Fas-mediated apoptosis both in vitro and in vivo, and is present in serum samples of patients with SLE. These results suggest a novel mechanism for resistance to apoptosis.
81. Hughes DP, Crispe IN. A naturally occurring soluble isoform of murine Fas generated by alternative splicing. of special interest J Exp Med. 182:1995;1395-1401 A variant, truncated form of Fas (Fas B) is cloned from murine thymocytes. This soluble form of Fas inhibits Fas-mediated apoptosis in vitro. Fas B is expressed abundantly in lymphoid tissue, suggesting that it may be involved in regulating Fas-dependent deletion. See also [2,40,41].
82. of special interest Natoli G, Ianni A, Costanzo A, DePetrillo G, Ilari I, Chirillo P, Balsano C, Levrero M. Resistance to Fas-mediated apoptosis in human hepatoma cells. Oncogene. 11:1995;1157-1164.
83. Cascino I, Papoff G, De Maria R, Testi R, Ruberti G. Fas/Apo-1 (CD95) receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis. of special interest J Immunol. 156:1996;13-17 A variant form of Fas lacking the intracellular death domain is found in human HUT78 lymphoma cells that are Fas resistant. This mutated Fas interferes with Fas-mediated apoptosis when expressed in COS cells along with wild-type Fas. Variant Fas may represent a mechanism by which malignant cells are protected against Fas-dependent killing.
84. L and Bcl-2, displaces Bax and promotes cell death. Cell. 80:1995;285-291.
85. Farrow SN, White JHM, Martinou I, Raven T, Pun K-T, Grinham CJ, Martinou J-C, Brown R. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature. 374:1995;731-733.
86. Chittenden T, Harrington EA, O'Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC. Induction of apoptosis by the Bcl-2 homologue Bak. Nature. 374:1995;733-736.
87. Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ. Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature. 374:1995;736-739.
88. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:1993;609-619.
89. Knudson CM, Tung KSK, Tourtellote WG, Brown GAJ, Korsmeyer SJ. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 270:1995;96-99.
90. Boise LH, González-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 74:1993;597-608.
91. Boyd JM, Gallo GJ, Elangovan B, Houghton AB, Malstrom S, Avery BJ, Ebb RG, Subramanian T, Chittenden T, Lutz R, Chinnadurai G. 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. 11:1995;1921-1928.
92. Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the EIB 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci USA. 89:1992;7742-7746.
93. Boldin MP, Varfolomeev EE, Pancer Z, Mett IL, Camonis JH, Wallach D. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem. 270:1995;7795-7798.
94. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 81:1995;505-512.
95. Chu K, Niu X, Williams LT. A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc Natl Acad Sci USA. 92:1995;11894-11898.
96. Tian Q, Taupin J-L, Elledge S, Robertson M, Anderson P. Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis. J Exp Med. 182:1995;865-874.
97. Su X, Zhou T, Wang Z, Yang P, Jope RS, Mountz JD. Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis. Immunity. 2:1995;353-362.
98. Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He W-W, Dixit VM. ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein Ced-3 is activated during Fas-and tumor necrosis factor-induced apoptosis. J Biol Chem. 271:1996;1621-1625.
99. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 75:1993;641-652.
100. Los M, Van de Craen M, Penning LC, Schenk H, Westendorp M, Baeuerle PA, Droge W, Krammer PH, Fiers W, Schulze-Osthoff K. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 375:1995;81-83.
101. Wang L, Miura M, Bergeron L, Zhu H, Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 78:1994;739-750.
102. Kumar S, Kinoshita M, Noda M, Copeland NG, Jenkins NA. Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1β-converting enzyme. Genes Dev. 8:1994;1613-1626.
103. Kamens J, Paskind M, Hugunin M, Talanian RV, Allen H, Banach D, Bump N, Hackett M, Johnston CG, Li P, et al. Identification and characterization of ICH-2, a novel member of the interleukin-1β-converting enzyme family of cysteine proteases. J Biol Chem. 270:1995;15250-15256.
104. Faucheu C, Diu A, Chan AW, Blanchet AM, Miossec C, Herve F, Collard-Dutilleul, Gu Y, Aldape RA, Lippke JA, et al. A novel human protease similar to the interleukin-1β converting enzyme induces apoptosis in transfected cells. EMBO J. 14:1995;1914-1922.
105. 2+-dependent endonuclease associated with apoptosis. J Immunol. 156:1996;922-931.
106. Shibahara K, Asano M, Ishida Y, Aoki T, Koike T, Honjo T. Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene. 166:1995;297-301.
107. Fernandes-Alnemri T, Litwack G, Alnemri ES. Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. Cancer Res. 55:1995;2737-2742.
108. Woronicz JD, Calnan B, Ngo V, Winoto A. Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature. 367:1994;277-281.
109. Liu ZG, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature. 367:1994;281-284.
110. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 352:1991;345-347.
111. Lahti JM, Xiang J, Heath LS, Campana D, Kidd VJ. PITSLRE protein kinase activity is associated with apoptosis. Mol Cell Biol. 15:1995;1-11.
112. White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H. Genetic control of programmed cell death in Drosophila. Science. 264:1994;677-683.
113. Stanger BZ, Leder P, Lee T-H, Kim E, Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell. 81:1995;513-523.
114. Hsu H, Shu H-B, Pan M-G, Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. of special interest Cell. 84:1996;299-308 TRAF2 and FADD are identified as TNF receptor 1-associated protein-(TRADD-) interacting proteins by yeast two hybrid screening, confirmed by immunoprecipitation. Different regions of TRADD bind TRAF2 and FADD, in particular the carboxy-terminal 'death' domain of TRADD is required for interaction with the 'death' domain expressing FADD. Although TRADD may simply be a linker protein coupling TNF-R1 and FADD, interacting proteins such as TRADD may influence the availability or function of mediators like FADD that carry death signaling from TNFR family members.
115. Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 269:1994;30761-30764.
116. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell. 81:1995;801-809.
117. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 376:1995;37-43.
118. Lin EY, Orlofsky A, Berger MS, Prystowsky MB. Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. J Immunol. 151:1993;1979-1988.
119. 12+-binding protein ALG-2 and Alzheimers disease gene ALG-3. Science. 271:1996;521-525.
120. Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC. Cloning and functional analysis of BAG-1: a novel Bcl-2 binding protein with anti-cell death activity. Cell. 80:1995;279-284.
121. L and Bcl-2 repress a common pathway of cell death. J Exp Med. 182:1995;821-828.
122. Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A. Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci USA. 90:1993;8479-8483.
123. Sugimoto A, Hozak RR, Nakashima T, Nishimoto T, Rothman JH. dad-1, an endogenous programmed cell death suppressor in Caenorhabditis elegans and vertebrates. EMBO J. 14:1995;4434-4441.
124. Hashimoto S, Ishii A, Yonehara S. The E1b oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int Immunol. 3:1991;343-351.
125. Gooding LR, Aquino L, Duerksen-Hughes PJ, Day D, Horton TM, Yei SP, Wold WS. The E1B 19,000-molecular-weight protein of group C adenoviruses prevents tumor necrosis factor cytolysis of human cells but not of mouse cells. J Virol. 65:1991;3083-3094.
126. Sato T, Irie S, Kitada S, Reed JC. FAP-1: a protein tyrosine phosphatase that associates with Fas. Science. 268:1995;411-415.
127. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci USA. 90:1993;3516-3520.
128. Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnson A, Lefebvre C, Kang X. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spiral muscular atrophy. Cell. 80:1995;167-178.
129. Sugimoto A, Friesen PD, Rothman JH. Baculovirus p35 prevents developmentally programmed cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans. EMBO J. 13:1994;2023-2028.
130. Yao R, Cooper GM. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science. 267:1995;2003-2006.
131. Moroy T, Grzeschiczek A, Petzold S, Hartmann KU. Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in mice. Proc Natl Acad Sci USA. 90:1993;10734-10738.
132. Schauer SL, Wang Z, Sonenshein GE, Rothstein TL. Maintenance of NF-κB and c-myc expression in CD40 rescue of receptor-mediated apoptosis of WEHI 231 early B cells. J Immunol. 1996;. in press.
133. Karras JG, Wang Z, Frank DA, Rothstein TL. Antigen receptor engagement in B cells induces nuclear expression of STAT5 and STAT6 proteins that bind and transactivate an IFN-γ activation site. J Immunol. 1996;. in press.