The BCR signalosome: Where cell fate is decided

Journal of Biological Regulators and Homeostatic Agents

Volumn 19, Issue 1-2, 2005, Pages 1-16

  Ulivieri, C ^a   Baldari, Cosima T ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

Costimulatory receptor; Inhibitory receptor; Lipid rafts; Molecular adaptor; Protein tyrosine kinase; Protein tyrosine phosphatase

Indexed keywords

B LYMPHOCYTE ANTIGEN; B LYMPHOCYTE ANTIGEN RECEPTOR; CD19 ANTIGEN; CD22 ANTIGEN; CD5 ANTIGEN; CELL PROTEIN; DIACYLGLYCEROL; FC RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INOSITOL 1,4,5 TRISPHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; PHOSPHOLIPASE C; PROTEIN BAM32; PROTEIN BCAP; PROTEIN BLNK; PROTEIN C JUN; PROTEIN CBP; PROTEIN GAB1; PROTEIN GAB2; PROTEIN LAB; PROTEIN PAG; PROTEIN SLP 65; PROTEIN TYROSINE PHOSPHATASE SHP 2; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR NFAT; UNCLASSIFIED DRUG;

CELL DEATH; CELL FATE; CELL MEMBRANE; CELL SURVIVAL; CYTOSOL; ENZYME ACTIVITY; HODGKIN DISEASE; LIPID RAFT; LYMPHOCYTE ACTIVATION; LYMPHOCYTE PROLIFERATION; NONHUMAN; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

EID: 26844470144     PISSN: 0393974X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (174)

1. Reth M. Oligomeric antigen receptors: A new view on signaling for the selection of lymphocytes. Trends Immunol 2001; 22: 356-60.
2. Matsuuchi L, Gold MR. New views of BCR structure and organization. Curr Opin Immunol 2001; 13: 270-7.
3. Foy SP, Matsuuchi L. Association of B lymphocyte antigen receptor polypeptides with multiple chaperone proteins. Immunol Lett 2001; 78: 149-60.
4. Williams GT, Dariavach P, Venkitaraman AR, Gilmore DJ, Neuberger MS. Membrane immunoglobulin without sheath or anchor. Mol Immunol 1993; 30: 1427-32.
5. Wu Y, Pun C, Hozumi N. Roles of calnexin and Ig-alpha beta interactions with membrane Igs in the surface expression of the B cell antigen receptor of the IgM and IgD classes. J Immunol 1997; 158: 2762-70.
6. Schamel WW, Reth M. Monomeric and oligomeric complexes of the B cell antigen receptor. Immunity 2000; 13: 5-14.
7. Kurosaki T. Genetic analysis of B cell antigen receptor signaling. Annu Rev Immunol 1999; 17: 555-92.
8. Pierce SK. Lipid rafts and B-cell activation. Nat Rev Immunol 2002; 2: 96-105.
9. Cheng PC, Dykstra ML, Mitchell RN, Pierce SK. A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J Exp Med 1999; 190: 1549-60.
10. Thyagarajan R, Arunkumar N, Song W. Polyvalent antigens stabilize B cell antigen receptor surface signaling microdomains. J Immunol 2003; 170: 6099-106.
11. Cheng PC, Brown BK, Song W, Pierce SK. Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling. J Immunol 2001; 166: 3693-701.
12. Sproul TW, Malapati S, Kim J, Pierce SK. Cutting edge: B cell antigen receptor signaling occurs outside lipid rafts in immature B cells. J Immunol 2000; 165: 6020-3.
13. Guo B, Kato RM, Garcia-Lloret M, Wahl MI, Rawlings DJ. Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex. Immunity 2000; 13: 243-53.
14. Goodnow CC, Crosbie J, Adelstein S, et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 1988; 334: 676-82.
15. Norvell A, Mandik L, Monroe JG. Engagement of the antigen-receptor on immature murine B lymphocytes results in death by apoptosis. J Immunol 1995; 154: 4404-13.
16. Young RM, Holowka D, Baird B. A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation. J Biol Chem 2003; 278: 20746-52.
17. Yanagi S, Sugawara H, Kurosaki M, Sabe H, Yamamura H, Kurosaki T. CD45 modulates phosphorylation of both autophosphorylation and negative regulatory tyrosines of Lyn in B cells. J Biol Chem 1996; 271: 30487-92.
18. Yu CC, Mamchak AA, DeFranco AL. Signaling mutations and autoimmunity. Curr Dir Autoimmun 2003; 6: 61-88.
19. Shrivastava P, Katagiri T, Ogimoto M, Mizuno K, Yakura H. Dynamic regulation of Src-family kinases by CD45 in B cells. Blood 2003 Oct 16 [Epub ahead of print].
20. Pritchard NR, Smith KG. B cell inhibitory receptors and autoimmunity. Immunology 2003; 108: 263-73.
21. Aman MJ, Tosello-Trampont AC, Ravichandran K. Fc gamma RIIB1/SHIP-mediated inhibitory signaling in B cells involves lipid rafts. J Biol Chem 2001; 276: 46371-8.
22. Pike LJ, Miller JM. Cholesterol depletion delocalizes phosphatidylinositol biphosphate and inhibits hormone-stimulated phosphatidylinositol turnover. J Biol Chem 1998; 273: 22298-304.
23. Takata M, Sabe H, Hata A, et al. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways. EMBO J 1994; 13: 1341-9.
24. Takata M, Homma Y, Kurosaki T. Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M-induced B cell apoptosis. J Exp Med 1995; 182: 907-14.
25. Wienands J, Schweikert J, Wolischeid B, Jumaa H, Nielsen PJ, Reth M. SLP-65: A new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J Exp Med 1998; 188: 791-5.
26. Goitsuka R, Fujimura Y, Mamada H, et al. BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius. J Immunol 1998; 161: 5804-8.
27. Gangi-Peterson L, Peterson SN, Shapiro LH, et al. bca: an activation-related B-cell gene. Mol Immunol 1998; 35: 55-63.
28. Fu C, Turck CW, Kurosaki T, Chan AC. BLNK: A central linker protein in B cell activation. Immunity 1998; 9: 93-103.
29. Campbell KS. Signal transduction from the B cell antigen-receptor. Curr Opin Immunol 1999; 11: 256-64.
30. Baba Y, Hashimoto S, Matsushita M, et al. BLNK mediates Syk-dependent Btk activation. Proc Natl Acad Sci USA 2001; 98: 2582-6.
31. Yasuda T, Maeda A, Kurosaki M, et al. Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma 2 binding. J Exp Med 2000; 191: 641-50.
32. Bustelo XR. Regulatory and signaling properties of the Vav family. Mol Cell Biol 2000; 20: 1461-77.
33. Hashimoto A, Okada H, Jiang A, et al. Involvement of guanosine triphosphatases and phospholipase C-gamma 2 in extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase activation by the B cell antigen receptor. J Exp Med 1998; 188: 1287-95.
34. Johmura S, Oh-hora M, Inabe K, et al. Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK. Immunity 2003; 18: 777-87.
35. Mizuno K, Tagawa Y, Mitomo K, et al. Src homology region 2 domain-containing phosphatase 1 positively regulates B cell receptor-induced apoptosis by modulating association of B cell linker protein with Nck and activation of c-Jun NH2-terminal kinase. J Immunol 2002; 169: 778-86.
36. Mizuno K, Tagawa Y, Mitomo K, et al. Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates B cell linker protein/SH2 domain leukocyte protein of 65 kDa and selectively regulates c-Jun NH2-terminal kinase activation in B cells. J Immunol 2000; 165: 1344-51.
37. Tan JE, Wong SC, Gan SK, Xu S, Lam KP. The adaptor protein BLNK is required for B cell antigen receptor-induced activation of nuclear factor-kappa B and cell cycle entry and survival of B lymphocytes. J Biol Chem 2001; 276: 20055-63.
38. Turner M, Mee PJ, Costello PS, et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 1995; 378: 298-302.
39. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 1995; 378: 303-6.
40. Fruman DA, Snapper SB, Yballe CM, et al. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85 alpha. Science 1999; 283: 393-7.
41. Suzuki H, Terauchi Y, Fujiwara M, et al. Xid-like immunodeficiency in mice with disruption of the p85alpha subunit ofphosphoinositide 3-kinase. Science 1999; 283: 390-2.
42. Hardy RR, Hayakawa K, Parks DR, Herzenberg LA. Demonstration of B-cell maturation in X-linked immunodeficient mice by simultaneous three-colour immunofluorescence. Nature 1983; 306: 270-2.
43. Khan WN, Alt FW, Gerstein RM, et al. Defective B cell development and Junction in Btk-deficient mice. Immunity 1995; 3: 283-99.
44. Xu S, Tan JE, Wong EP, Manickam A, Ponniah S, Lam KP. B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice. Int Immunol 2000; 12: 397-404.
45. Jumaa H, Bossaller L, Portugal K, et al. Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia. Nature 2003; 423: 452-6.
46. Marafioti T, Pozzobon M, Hansmann ML, Delsol G, Pileri SA, Mason DY. Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease. Blood 2004; 103: 188-93.
47. Kandel ES, Hay N. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp Cell Res 1999; 253: 210-29.
48. Varnai P, Rother KI, Balla T. Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells. J Biol Chem 1999; 274: 10983-9.
49. Falasca M, Logan SK, Lehto VP, Baccante G, Lemmon MA, Schlessinger J. Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting. EMBO J 1998; 17: 414-22.
50. van Noesel CJ, Lankester AC, van Schijndel GM, van Lier RA. The CR2/CD19 complex on human B cells contains the src-family kinase Lyn. Int Immunol 1993; 5: 699-705.
51. Fujimoto M, Poe JC, Jansen PJ, Sato S, Tedder TF. CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation. J Immunol 1999; 162: 7088-94.
52. Maroun CR, Holgado-Madruga M, Royal I, et al. The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol Cell Biol 1999; 19: 1784-99.
53. Okada T, Maeda A, Iwamatsu A, Gotoh K, Kurosaki T. BCAP: The tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity 2000; 13: 817-27.
54. Nishida K, Yoshida Y, Itoh M, et al. Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors. Blood 1999; 93: 1809-16.
55. Ingham RJ, Holgado-Madruga M, Siu C, Wong AJ, Gold MR. The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor. J Biol Chem 1998; 273: 30630-7.
56. Ingham RJ, Santos L, Dang-Lawson M, et al. The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. J Biol Chem 2001; 276: 12257-65.
57. Gu H, Pratt JC, Burakoff SJ, Neel BG. Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Mol Cell 1998; 2: 729-40.
58. Gold MR, Ingham RJ, McLeod SJ, et al. Targets of B-cell antigen receptor signaling: The phosphatidylinositol 3-kinase/Akt/glycogensynthase kinase-3 signaling pathway and the Rap1 GTPase. Immunol Rev 2000; 176: 47-68.
59. Tognon CE, Kirk HE, Passmore LA, Whitehead IP, Der CJ, Kay RJ. Regulation of RasGRP via a phorbol ester-responsive C1 domain. Mol Cell Biol 1998; 18: 6995-7008.
60. Inabe K, Kurosaki T. Tyrosine phosphorylation of B-cell adaptor for phosphoinositide 3-kinase is required for Akt activation in response to CD19 engagement. Blood 2002; 99: 584-9.
61. Yamazaki T, Takeda K, Gotoh K, Takeshima H, Akira S, Kurosaki T. Essential immunoregulatory role for BCAP in B cell development and function. J Exp Med 2002; 195: 535-45.
62. Yamazaki T, Kurosaki T. Contribution of BCAP to maintenance of mature B cells through c-Rel. Nat Immunol 2003; 4: 780-6.
63. Marshall AJ, Niiro H, Lerner CG, et al. A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase. J Exp Med 2000; 191: 1319-32.
64. Niiro H, Maeda A, Kurosaki T, Clark EA. The B lymphocyte adaptor molecule of 32 kD (Bam32) regulates B cell antigen receptor signaling and cell survival. J Exp Med 2002; 195: 143-9.
65. Han A, Saijo K, Mecklenbrauker I, Tarakhovsky A, Nussenzweig MC. Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival. Immunity 2003; 19: 621-32.
66. Brdicka T, Imrich M, Angelisova P, et al. Non-T cell activation linker (NTAL): A transmembrane adaptor protein involved in immunoreceptor signaling. J Exp Med 2002; 196: 1617-26.
67. Janssen E, Zhu M, Zhang W, Koonpaew S, Zhang W. LAB: A new membrane-associated adaptor molecule in B cell activation. Nat Immunol 2003; 4: 117-23.
68. Brdicka T, Pavlistova D, Leo A, et al. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein-tyrosine kinase csk and is involved in regulation of T cell activation. J Exp Med 2000; 191: 1591-604.
69. Takeuchi S, Takayama Y, Ogawa A, Tamura K, Okada M. Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl-terminal Src kinase, Csk. J Biol Chem 2000; 275: 29183-6.
70. Kawabuchi M, Satomi Y, Takao T, et al. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature 2000; 404: 999-1003.
71. Davidson D, Bakinowski M, Thomas ML, Horejsi V, Veillette A. Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol Cell Biol 2003; 23: 2017-28.
72. Kurosaki T. Regulation of B-cell signal transduction by adaptor proteins. Nat Rev Immunol 2002; 2: 354-63.
73. Tedder TF. Introduction: Response-regulators of B lymphocyte signaling thresholds provide a context for antigen receptor signal transduction. Semin Immunol 1998; 10: 259-65.
74. Tedder TF, Inaoki M, Sato S. The CD19-CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity 1997; 6: 107-18.
75. Bradbury LE, Goldmacher VS, Tedder TF. The CD19 signal transduction complex of B lymphocytes. Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13. J Immunol 1993; 151: 2915-27.
76. Weis JJ, Tedder TF, Fearon DT. Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. Proc Natl Acad Sci USA 1984; 81: 881-5.
77. van Noesel CJ, Lankester AC, van Lier RA. Dual antigen recognition by B cells. Immunol Today 1993; 14: 8-11.
78. Tedder TF, Haas KM, Poe JC. CD19-CD21 complex regulates an intrinsic Src family kinase amplification loop that links innate immunity with B-lymphocyte intracellular calcium responses. Biochem Soc Trans 2002; 30: 807-11.
79. Hasegawa M, Fujimoto M, Poe JC, Steeber DA, Tedder TF. CD19 can regulate B lymphocyte signal transduction independent of complement activation. J Immunol 2001; 167: 3190-200.
80. Cheng PC, Cherukuri A, Dykstra M, et al. Floating the raft hypothesis: The roles of lipid rafts in B cell antigen receptor function. Semin Immunol 2001; 13: 107-14.
81. Cherukuri A, Shoham T, Sohn HW, et al. The tetraspanin CD81 is necessary for partitioning of colligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts. J Immunol 2004; 172: 370-80.
82. Cherukuri A, Cheng PC, Sohn HW, Pierce SK. The CD19/CD21 complex functions to prolong B cell antigen receptor signaling from lipid rafts. Immunity 2001; 14: 169-79.
83. Fearon DT, Carroll MC. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol 2000; 18: 393-422.
84. Fujimoto M, Poe JC, Hasegawa M, Tedder TF. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol Res 2000; 22: 281-98.
85. Fujimoto M, Fujimoto Y, Poe JC, et al. CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 2000; 13: 47-57.
86. Xu Y, Beavitt SJ, Harder KW, Hibbs ML, Tarlinton DM. The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent. J Immunol 2002; 169: 6910-8.
87. Sen G, Wu HJ, Bikah G, et al. Defective CD19-dependent signaling in B-1a and B-1b B lymphocyte subpopulations. Mol Immunol 2002; 39: 57-68.
88. Wilson GL, Fox CH, Fauci AS, Kehrl JH. cDNA cloning of the B cell membrane protein CD22: A mediator of B-B cell interactions. J Exp Med 1991; 173: 137-46.
89. Powell LD, Sgroi D, Sjoberg ER, Stamenkovic I, Varki A. Natural ligands of the B cell adhesion molecule CD22 beta carry N-linked oligosaccharides with alpha-2,6-linked sialic acids that are required for recognition. J Biol Chem 1993; 268: 7019-27.
90. Crocker PR. Siglecs: Sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signaling. Curr Opin Struct Biol 2002; 12: 609-15.
91. Danzer CP, Collins BE, Blixt O, Paulson JC, Nitschke L. Transitional and marginal zone B cells have a high proportion of unmasked CD22: Implications for BCR signaling. Int Immunol 2003; 15: 1137-47.
92. Lanoue A, Batista FD, Stewart M, Neuberger MS. Interaction of CD22 with alpha2,6-linked sialoglycoconjugates: Innate recognition of self to dampen B cell autoreactivity? Eur J Immunol 2002; 32: 348-55.
93. Nitschke L, Floyd H, Ferguson DJ, Crocker PR. Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B cells. J Exp Med 1999; 189: 1513-8.
94. Razi N, Varki A. Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes. Proc Natl Acad Sci USA 1998; 95: 7469-74.
95. Kelm S, Gerlach J, Brossmer R, Danzer CP, Nitschke L. The ligand-binding domain of CD22 is needed for inhibition of the B cell receptor signal, as demonstrated by a novel human CD22-specific inhibitor compound. J Exp Med 2002; 195: 1207-13.
96. Jin L, McLean PA, Neel BG, Wortis HH. Sialic acid binding domains of CD22 are required for negative regulation of B cell receptor signaling. J Exp Med 2002; 195: 1199-205.
97. Doody GM, Justement LB, Delibrias CC, et al. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 1995 14; 269: 242-4.
98. Smith KG, Tarlinton DM, Doody GM, Hibbs ML, Fearon DT. Inhibition of the B cell by CD22: A requirement for Lyn. J Exp Med 1998; 187: 807-11.
99. Otipoby KL, Draves KE, Clark EA. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. J Biol Chem 2001; 276: 44315-22.
100. Smith KG, Fearon DT. Receptor modulators of B-cell receptor signaling-CD19/CD22. Curr Top Microbiol Immunol 2000; 245: 195-212.
101. O'Keefe TL, Williams GT, Davies SL, Neuberger MS. Hyperresponsive B cells in CD22-deficient mice. Science 1996; 274: 798-801.
102. Chan VW, Meng F, Soriano P, DeFranco AL, Lowell CA. Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation. Immunity 1997; 7: 69-81.
103. Shultz LD, Schweitzer PA, Rajan TV, et al. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 1993; 73: 1445-54.
104. Kozlowski M, Mlinaric-Rascan I, Feng GS, Shen R, Pawson T, Siminovitch KA. Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice. J Exp Med 1993; 178: 2157-63.
105. Tsui HW, Siminovitch KA, de Souza L, Tsui FW. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet 1993; 4: 124-9.
106. Hasler P, Zouali M. B cell receptor signaling and autoimmunity. FASEB J 2001; 15: 2085-98.
107. Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T. SHP-1 requires inhibitory coreceptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. J Biol Chem 2001; 276: 26648-55.
108. Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF. CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. J Biol Chem 2000; 275: 17420-7.
109. Harmer SL, DeFranco AL. The Src homology domain 2-containing inositol phosphatase SHIP forms a ternary complex with Shc and Grb2 in antigen receptor-stimulated B lymphocytes. J Biol Chem 1999; 274: 12183-91.
110. Jiang A, Craxton A, Kurosaki T, Clark EA. Different protein tyrosine kinases are required for B cell antigen receptor-mediated activation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase 1, and p38 mitogen-activated protein kinase. J Exp Med 1998; 188: 1297-306.
111. Coggeshall KM. Inhibitory signaling by B cell Fc gamma RIIb. Curr Opin Immunol 1998; 10: 306-12.
112. Ono M, Okada H, Bolland S, Yanagi S, Kurosaki T, Ravetch JV. Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 1997; 90: 293-301.
113. DeFranco AL. The complexity of signaling pathways activated by the BCR. Curr Opin Immunol 1997; 9: 296-308.
114. Gold MR, Scheid MP, Santos L, et al. The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. J Immunol 1999; 163: 1894-905.
115. Tamir I, Stolpa JC, Helgason CD, et al. The RasGAP-binding protein p62dok is a mediator of inhibitory FcgammaRIIB signals in B cells. Immunity 2000; 12: 347-58.
116. Helgason CD, Damen JE, Rosten P, et al. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev 1998; 12: 1610-20.
117. Sato K, Ochi A. Superclustering of B cell receptor and Fc gamma RIIB1 activates Src homology 2-containing protein tyrosine phosphatase-1. J Immunol 1998; 161: 2716-22.
118. Chacko GW, Tridandapani S, Damen JE, Liu L, Krystal G, Coggeshall KM. Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5 phosphatase, SHIP. J Immunol 1996; 157: 2234-8.
119. Tridandapani S, Chacko GW, Van Brocklyn JR, Coggeshall KM. Negative signaling in B cells causes reduced Ras activity by reducing Shc-Grb2 interactions. J Immunol 1997; 158: 1125-32.
120. Tridandapani S, Pradhan M, LaDine JR, Garber S, Anderson CL, Coggeshall KM. Protein interactions of Src homology 2 (SH2) domain-containing inositol-phosphatase (SHIP): Association with Shc displaces SHIP from FcgammaRIIb in Bcells. J Immunol 1999; 162: 1408-14.
121. Tridandapani S, Phee H, Shivakumar L, Kelley TW, Coggeshall KM. Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells. Mol Immunol 1998; 35: 1135-46.
122. Perez-Villar JJ, Whitney GS, Bowen MA, Hewgill DH, Aruffo AA, Kanner SB. CD5 negatively regulates the T-cell antigen receptor signal transduction pathway: Involvement of SH2-containing phosphotyrosine phosphatase SHP-1. Mol Cell Biol 1999; 19: 2903-12.
123. Gary-Gouy H, Bruhns P, Schmitt C, Dalloul A, Daeron M, Bismuth G. The pseudo-immunoreceptor tyrosine-based activation motif of CD5 mediates its inhibitory action on B-cell receptor signaling. J Biol Chem 2000; 275: 548-56.
124. Gary-Gouy H, Harriague J, Dalloul A, Donnadieu E, Bismuth G. CD5-negative regulation of B cell receptor signaling pathways originates from tyrosine residue Y429 outside an immunoreceptor tyrosine-based inhibitory motif. J Immunol 2002; 168: 232-9.
125. Sen G, Bikah G, Venkataraman C, Bondada S. Negative regulation of antigen receptor-mediated signaling by constitutive association of CD5 with the SHP-1 protein tyrosine phosphatase in B-1 B cells. Eur J Immunol 1999; 29: 3319-28.
126. Wong SC, Chew WK, Tan JE, Melendez AJ, Francis F, Lam KP. Peritoneal CD5+ B-1 cells have signaling properties similar to tolerant B cells. J Biol Chem 2002; 277: 30707-15.
127. Majolini MB, D'Elios MM, Galieni P, et al. Expression of the T-cell-specific tyrosine kinase Lck in normal B-1 cells and in chronic lymphocytic leukemia B cells. Blood 1998; 91: 3390-6.
128. Chiorazzi N, Ferrarini M. B cell chronic lymphocytic leukemia: Lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol 2003; 21: 841-94.
129. Bignon JS, Siminovitch KA. Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: A step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function. Clin Immunol Immunopathol 1994; 73: 168-79.
130. Tsui FW, Tsui HW. Molecular basis of the motheaten phenotype. Immunol Rev 1994; 138: 185-206.
131. -/- mice. Eur J Immunol 2003; 33: 441-5.
132. Lam KP, Rajewsky K. B cell antigen receptor specificity and surface density together determine B-1versus B-2 cell development. J Exp Med 1999; 190: 471-7.
133. Qian Y, Santiago C, Borrero M, Tedder TF, Clarke SH. Lupus-specific antiribonucleoprotein B cell tolerance in non autoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds. J Immunol 2001; 166: 2412-9.
134. Raab M, Yamamoto M, Rudd CE. The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck. Mol Cell Biol 1994; 14: 2862-70.
135. Goodman PA, Wood CM, Vassilev A, Mao C, Uckun FM. Spleen tyrosine kinase (Syk) deficiency in childhood pro-B cell acute lymphoblastic leukemia. Oncogene 2001; 20: 3969-78.
136. -/-mice. J Leukoc Biol 1994; 56: 812-6.
137. Hibbs ML, Tarlinton DM, Armes J, et al. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 1995; 83: 301-11.
138. Nishizumi H, Taniuchi I, Yamanashi Y, et al. Impaired proliferation of peripheral B cells and indication of autoimmune disease in Lyn-deficient mice. Immunity 1995; 3: 549-60.
139. Takeshita H, Taniuchi I, Kato J, Watanabe T. Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene. Int Immunol 1998; 10: 435-44.
140. Liossis SN, Solomou EE, Dimopoulos MA, Panayiotidis P, Mavrikakis MM, Sfikakis PP. B-cell kinase Lyn deficiency in patients with systemic lupus erythematosus. J Investig Med 2001; 49: 157-65.
141. Buhl AM, Cambier JC. Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated activation of Bruton's tyrosine kinase. J Immunol 1999; 162: 4438-46.
142. Tsukada S, Saffran DC, Rawlings DJ, et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993; 72: 279-90.
143. Vetrie D, Vorechovsky I, Sideras P, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature 1993; 361: 226-33.
144. Nishida K, Hirano T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci 2003; 94: 1029-33.
145. Itoh S, Itoh M, Nishida K, et al. Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal zone B cells and negatively regulates thymus-independent antigen-2 responses. J Immunol 2002; 168: 5110-6.
146. Walmsley MJ, Ooi SK, Reynolds LF, et al. Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science 2003; 302: 459-62.
147. Cyster JG, Goodnow CC. Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity 1995; 2:1 3-24.
148. Shultz LD, Schweitzer PA, Rajan TV, et al. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 1993; 73: 1445-54.
149. Qu CK, Nguyen S, Chen J, Feng GS. Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development. Blood 2001; 97: 911-4.
150. Liu Q, Oliveira-Dos-Santos AJ, Mariathasan S, et al. The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling. J Exp Med 1998; 188: 1333-42.
151. Brauweiler A, Tamir I, Dal Porto J, et al. Differential regulation of B cell development, activation, and death by the Src homology 2 domain-containing 5′ inositol phosphatase (SHIP). J Exp Med 2000; 191: 1545-54.
152. -/- mice. J Exp Med 2000; 191: 781-94.
153. Scharenberg AM, El-Hillal O, Fruman DA, et al. Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: A target for SHIP-mediated inhibitory signals. EMBO J 1998; 17: 1961-72.
154. Hashimoto A, Takeda K, Inaba M, et al. Cutting edge: Essential role of phospholipase C-gamma 2 in B cell development and function. J Immunol 2000; 165: 1738-42.
155. Tarakhovsky A, Turner M, Schaal S, et al. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 1995; 374: 467-70.
156. Zhang R, Alt FW, Davidson L, Orkin SH, Swat W. Defective signaling through the T- and B-cell antigen receptors in lymphoid cells lacking the Vav proto-oncogene. Nature 1995; 374: 470-3.
157. Cyster JG, Healy JI, Kishihara K, et al. Regulation of B lymphocyte negative and positive selection by tyrosine phosphatase CD45- Nature 1996; 381: 325-8.
158. Benatar T, Carsetti R, Furlonger C, Kamalia N, Mak T, Paige CJ. Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice. J Exp Med 1996; 183: 329-34.
159. Huck S, Le Corre R, Youinou P, Zouali M. Expression of B cell receptor-associated signaling molecules in human lupus. Autoimmunity 2001; 33: 213-24.
160. Kung C, Pingel JT, Heikinheimo M, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med 2000; 6: 343-5.
161. Engel P, Zhou LJ, Ord DC, et al. Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 1995; 3: 39-50.
162. Sato S, Ono N, Steeber DA, Pisetsky DS, Tedder TF. CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J Immunol 1996; 157: 4371-8.
163. Sato S, Miller AS, Inaoki M, Bock CB, Jansen PJ, Tang ML, Tedder TF. CD22 is both a positive and negative regulator of B lymphocyte antigen receptor signal transduction: Altered signaling in CD22-deficient mice. Immunity 1996; 5: 551-62.
164. O'Keefe TL, Williams GT, Batista FD, Neuberger MS. Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. J Exp Med 1999; 189: 1307-13.
165. -/- mice: Enhanced affinity maturation but impaired antibody persistence. J Immunol 2000; 164: 4522-32.
166. Molina H, Holers VM, Li B, et al. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci USA 1996; 93: 3357-61.
167. Boackle SA, Holers VM. Role of complement in the development of autoimmunity. Curr Dir Autoimmun 2003; 6: 154-68.
168. Maecker HT, Do MS, Levy S. CD81 on B cells promotes interleukin 4 secretion and antibody production during T helper type 2 immune responses. Proc Natl Acad Sci USA 1998; 95: 2458-62.
169. Nakamura A, Yuasa T, Ujike A, et al. Fcgamma receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease. J Exp Med 2000; 191: 899-906.
170. Bolland S, Yim YS, Tus K, Wakeland EK, Ravetch JV. Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(-/-) mice. J Exp Med 2002; 195: 1167-74.
171. Bolland S, Ravetch JV. Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 2000; 13: 277-85.
172. Torres RM, Flaswinkel H, Reth M, Rajewsky K. Aberrant B cell development and immune response in mice with a compromised BCR complex. Science 1996; 272:1 804-8.
173. Gong S, Nussenzweig MC. Regulation of an early developmental checkpoint in the B cell pathway by Igbeta. Science 1996; 272: 411-4.
174. Alfarano A, Indraccolo S, Circosta P, et al. An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. Blood 1999; 93: 2327-35.