B cell antigen receptor signaling 101

Molecular Immunology

Volumn 41, Issue 6-7, 2004, Pages 599-613

  Dal Porto, Joseph M ^a   Gauld, Stephen B ^a   Merrell, Kevin T ^a   Mills, David ^a   Pugh Bernard, Aimee E ^a   Cambier, John ^a  

^a NATIONAL JEWISH MEDICAL AND RESEARCH CENTER   (United States)

Author keywords

B cell antigen receptor; Co receptors; Ig ; MAPKinase; Membrane immunoglobulin; Signal transduction; Transcription factors; Tyrosine kinase

Indexed keywords

B LYMPHOCYTE ANTIGEN; LYMPHOCYTE ANTIGEN RECEPTOR;

ANTIBODY PRODUCTION; B LYMPHOCYTE; CELL MATURATION; CELL SURVIVAL; CELLULAR IMMUNITY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

EID: 3042522852     PISSN: 01615890     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molimm.2004.04.008     Document Type: Article

References (192)

1. Aagaard-Tillery K.M., Jelinek D.F. Phosphatidylinositol 3-kinase activation in normal human B lymphocytes. J. Immunol. 156:1996;4543-4554
2. Allman D., Lindsley R.C., DeMuth W., Rudd K., Shinton S.A., Hardy R.R. Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation. J. Immunol. 167:2001;6834-6840
3. Andjelkovic M., Alessi D.R., Meier R., Fernandez A., Lamb N.J., Frech M., Cron P., Cohen P., Lucocq J.M., Hemmings B.A. Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272:1997;31515-31524
4. Antony P., Petro J.B., Carlesso G., Shinners N.P., Lowe J., Khan W.N. B cell receptor directs the activation of NFAT and NF-kappaB via distinct molecular mechanisms. Exp. Cell Res. 291:2003;11-24
5. Astoul E., Watton S., Cantrell D. The dynamics of protein kinase B regulation during B cell antigen receptor engagement. J. Cell Biol. 145:1999;1511-1520
6. Bannish G., Fuentes-Panana E.M., Cambier J.C., Pear W.S., Monroe J.G. Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis. J. Exp. Med. 194:2001;1583-1596
7. Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science. 275:1997;1930-1934
8. Beitz L.O., Fruman D.A., Kurosaki T., Cantley L.C., Scharenberg A.M. SYK is upstream of phosphoinositide 3-kinase in B cell receptor signaling. J. Biol. Chem. 274:1999;32662-32666
9. Bellacosa A., Chan T.O., Ahmed N.N., Datta K., Malstrom S., Stokoe D., McCormick F., Feng J., Tsichlis P. Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene. 17:1998;313-325
10. Benatar T., Carsetti R., Furlonger C., Kamalia N., Mak T., Paige C.J. Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice. J. Exp. Med. 183:1996;329-334
11. Benschop R.J., Aviszus K., Zhang X., Manser T., Cambier J.C., Wysocki L.J. Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive. Immunity. 14:2001;33-43
12. Benschop R.J., Melamed D., Nemazee D., Cambier J.C. Distinct signal thresholds for the unique antigen receptor-linked gene expression programs in mature and immature B cells. J. Exp. Med. 190:1999;749-756
13. Bikah G., Carey J., Ciallella J.R., Tarakhovsky A., Bondada S. CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science. 274:1996;1906-1909
14. Blasioli J., Paust S., Thomas M.L. Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. J. Biol. Chem. 274:1999;2303-2307
15. Blery M., Kubagawa H., Chen C.C., Vely F., Cooper M.D., Vivier E. The paired Ig-like receptor PIR-B is an inhibitory receptor that recruits the protein-tyrosine phosphatase SHP-1. Proc. Natl. Acad. Sci. U.S.A. 95:1998;2446-2451
16. Brdicka T., Pavlistova D., Leo A., Bruyns E., Korinek V., Angelisova P., Scherer J., Shevchenko A., Hilgert I., Cerny J., Drbal K., Kuramitsu Y., Kornacker B., Horejsi V., Schraven B. 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. 191:2000;1591-1604
17. Brennan P., Babbage J.W., Burgering B.M., Groner B., Reif K., Cantrell D.A. Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity. 7:1997;679-889
18. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:1999;857-868
19. Buhl A.M., Cambier J.C. 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. 162:1999;4438-4446
20. Buhl A.M., Pleiman C.M., Rickert R.C., Cambier J.C. Qualitative regulation of B cell antigen receptor signaling by CD19: selective requirement for PI3-kinase activation, inositol-1, 4, 5-trisphosphate production and Ca2+ mobilization. J. Exp. Med. 186:1997;1897-1910
21. Caldwell R.G., Wilson J.B., Anderson S.J., Longnecker R. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity. 9:1998;405-411
22. Cambier J.C. New nomenclature for the Reth motif (or ARH1/TAM/ARAM/YXXL). Immunol. Today. 16:1995;110
23. Cambier J.C., Kettman J.R., Vitetta E.S., Uhr J.W. Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance. J. Exp. Med. 144:1976;293-297
24. Cantrell D. Protein kinase B (Akt) regulation and function in T lymphocytes. Semin. Immunol. 14:2002;19-26
25. Carsetti R., Kohler G., Lamers M.C. Transitional B cells are the target of negative selection in the B cell compartment. J. Exp. Med. 181:1995;2129-2140
26. Carter R.H., Doody G.M., Bolen J.B., Fearon D.T. Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex. J. Immunol. 158:1997;3062-3069
27. Casola S., Otipoby K.L., Alimzhanov M., Humme S., Uyttersprot N., Kutok J.L., Carroll M.C., Rajewsky K. B cell receptor signal strength determines B cell fate. Nat. Immunol. 5:2004;317-327
28. Chan V.W., Lowell C.A., DeFranco A.L. Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes. Curr. Biol. 8:1998;545-553
29. Chan V.W., Meng F., Soriano P., DeFranco A.L., Lowell C.A. Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation. Immunity. 7:1997;69-81
30. Cheng A.M., Rowley B., Pao W., Hayday A., Bolen J.B., Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 378:1995;303-306
31. Cheng P.C., Brown B.K., Song W., Pierce S.K. Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling. J. Immunol. 166:2001;3693-3701
32. Cheng P.C., Dykstra M.L., Mitchell R.N., Pierce S.K. A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J. Exp. Med. 190:1999;1549-1560
33. Cherukuri A., Shoham T., Sohn H.W., Levy S., Brooks S., Carter R., Pierce S.K. The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts. J. Immunol. 172:2004;370-380
34. Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C. BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins. EMBO J. 21:2002;6461-6472
35. Chumley M.J., Dal Porto J.M., Cambier J.C. The unique antigen receptor signaling phenotype of B-1 cells is influenced by locale but induced by antigen. J. Immunol. 169:2002;1735-1743
36. Chung J.B., Baumeister M.A., Monroe J.G. Cutting edge: differential sequestration of plasma membrane-associated B cell antigen receptor in mature and immature B cells into glycosphingolipid-enriched domains. J. Immunol. 166:2001;736-740
37. Chung J.B., Silverman M., Monroe J.G. Transitional B cells: step by step towards immune competence. Trends Immunol. 24:2003;343-349
38. Clark M.R., Campbell K.S., Kazlauskas A., Johnson S.A., Hertz M., Potter T.A., Pleiman C., Cambier J.C. The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors. Science. 258:1992;123-126
39. Cornall R.J., Cyster J.G., Hibbs M.L., Dunn A.R., Otipoby K.L., Clark E.A., Goodnow C.C. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity. 8:1998;497-508
40. Craxton A., Jiang A., Kurosaki T., Clark E.A. Syk and Bruton's tyrosine kinase are required for B cell antigen receptor-mediated activation of the kinase Akt. J. Biol. Chem. 274:1999;30644-30650
41. Cross D.A., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:1995;785-789
42. Cyster J.G., Goodnow C.C. Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity. 2:1995;13-24
43. Cyster J.G., Goodnow C.C. Tuning antigen receptor signaling by CD22: integrating cues from antigens and the microenvironment. Immunity. 6:1997;509-517
44. D'Ambrosio D., Hippen K.L., Cambier J.C. Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor. Eur. J. Immunol. 26:1996;1960-1965
45. Datta K., Franke T.F., Chan T.O., Makris A., Yang S.I., Kaplan D.R., Morrison D.K., Golemis E.A., Tsichlis P.N. AH/PH domain-mediated interaction between Akt molecules and its potential role in Akt regulation. Mol. Cell. Biol. 15:1995;2304-2310
46. Datta S.R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y., Greenberg M.E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:1997;231-241
47. Davis R.S., Dennis G. Jr., Odom M.R., Gibson A.W., Kimberly R.P., Burrows P.D., Cooper M.D. Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family. Immunol. Rev. 190:2002;123-136
48. del Peso L., Gonzalez-Garcia M., Page C., Herrera R., Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 278:1997;687-689
49. Dolmetsch R.E., Lewis R.S., Goodnow C.C., Healy J.I. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature. 386:1997;855-858
50. Dong C., Davis R.J., Flavell R.A. MAP kinases in the immune response. Annu. Rev. Immunol. 20:2002;55-72
51. Ehrhardt G.R., Davis R.S., Hsu J.T., Leu C.M., Ehrhardt A., Cooper M.D. The inhibitory potential of Fc receptor homolog 4 on memory B cells. Proc. Natl. Acad. Sci. U.S.A. 100:2003;13489-13494
52. Engel P., Zhou L.J., Ord D.C., Sato S., Koller B., Tedder T.F. Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity. 3:1995;39-50
53. Engels N., Wollscheid B., Wienands J. Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha. Eur. J. Immunol. 31:2001;2126-2134
54. Famiglietti S.J., Nakamura K., Cambier J.C. Unique features of SHIP, SHP-1 and SHP-2 binding to FcgammaRIIb revealed by surface plasmon resonance analysis. Immunol. Lett. 68:1999;35-40
55. Fearon D.T., Carter R.H. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu. Rev. Immunol. 13:1995;127-149
56. Flaswinkel H., Reth M. Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor. EMBO J. 13:1994;83-89
57. Fong D.C., Brauweiler A., Minskoff S.A., Bruhns P., Tamir I., Mellman I., Daeron M., Cambier J.C. Mutational analysis reveals multiple distinct sites within Fc gamma receptor IIB that function in inhibitory signaling. J. Immunol. 165:2000;4453-4462
58. Fournier E., Isakoff S.J., Ko K., Cardinale C.J., Inghirami G.G., Li Z., de Lafaille M.A., Skolnik E.Y. The B cell SH2/PH domain-containing adaptor Bam32/DAPP1 is required for T cell-independent II antigen responses. Curr. Biol. 13:2003;1858-1866
59. Frech M., Andjelkovic M., Ingley E., Reddy K.K., Falck J.R., Hemmings B.A. High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272:1997;8474-8481
60. Fruman D.A., Snapper S.B., Yballe C.M., Davidson L., Yu J.Y., Alt F.W., Cantley L.C. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science. 283:1999;393-397
61. Fu C., Turck C.W., Kurosaki T., Chan A.C. BLNK: a central linker protein in B cell activation. Immunity. 9:1998;93-103
62. Fujimoto M., Bradney A.P., Poe J.C., Steeber D.A., Tedder T.F. Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop. Immunity. 11:1999;191-200
63. Fujimoto M., Fujimoto Y., Poe J.C., Jansen P.J., Lowell C.A., DeFranco A.L., Tedder T.F. CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity. 13:2000;47-57
64. Fujimoto M., Poe J.C., Inaoki M., Tedder T.F. CD19 regulates B lymphocyte responses to transmembrane signals. Semin. Immunol. 10:1998;267-277
65. Garcia-Cozar F.J., Okamura H., Aramburu J.F., Shaw K.T., Pelletier L., Showalter R., Villafranca E., Rao A. Two-site interaction of nuclear factor of activated T cells with activated calcineurin. J. Biol. Chem. 273:1998;23877-23883
66. Gauld S.B., Blair D., Moss C.A., Reid S.D., Harnett M.M. Differential roles for extracellularly regulated kinase-mitogen-activated protein kinase in B cell antigen receptor-induced apoptosis and CD40-mediated rescue of WEHI-231 immature B cells. J. Immunol. 168:2002;3855-3864
67. Goitsuka R., Fujimura Y., Mamada H., Umeda A., Morimura T., Uetsuka K., Doi K., Tsuji S., Kitamura D. BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius. J. Immunol. 161:1998;5804-5808
68. Gold M.R., Chan V.W., Turck C.W., DeFranco A.L. Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B lymphocytes. J. Immunol. 148:1992;2012-2022
69. Gold M.R., Ingham R.J., McLeod S.J., Christian S.L., Scheid M.P., Duronio V., Santos L., Matsuuchi L. Targets of B-cell antigen receptor signaling: the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway and the Rap1 GTPase. Immunol. Rev. 176:2000;47-68
70. Goodnow C.C., Crosbie J., Adelstein S., Lavoie T.B., Smith-Gill S.J., Brink R.A., Pritchard-Briscoe H., Wotherspoon J.S., Loblay R.H., Raphael K., et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 334:1988;676-682
71. Han A., Saijo K., Mecklenbrauker I., Tarakhovsky A., Nussenzweig M.C. Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival. Immunity. 19:2003;621-632
72. Hara H., Wada T., Bakal C., Kozieradzki I., Suzuki S., Suzuki N., Nghiem M., Griffiths E.K., Krawczyk C., Bauer B., D'Acquisto F., Ghosh S., Yeh W.C., Baier G., Rottapel R., Penninger J.M. The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity. 18:2003;763-775
73. Hasegawa M., Fujimoto M., Poe J.C., Steeber D.A., Tedder T.F. CD19 can regulate B lymphocyte signal transduction independent of complement activation. J. Immunol. 167:2001;3190-3200
74. Hashimoto A., Okada H., Jiang A., Kurosaki M., Greenberg S., Clark E.A., Kurosaki T. Involvement of guanosine triphosphatases and phospholipase C-gamma2 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. 188:1998;1287-1295
75. Hashimoto S., Iwamatsu A., Ishiai M., Okawa K., Yamadori T., Matsushita M., Baba Y., Kishimoto T., Kurosaki T., Tsukada S. Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK - functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling. Blood. 94:1999;2357-2364
76. Hata A., Sabe H., Kurosaki T., Takata M., Hanafusa H. Functional analysis of Csk in signal transduction through the B-cell antigen receptor. Mol. Cell. Biol. 14:1994;7306-7313
77. Hayami K., Fukuta D., Nishikawa Y., Yamashita Y., Inui M., Ohyama Y., Hikida M., Ohmori H., Takai T. Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. J. Biol. Chem. 272:1997;7320-7327
78. Healy J.I., Dolmetsch R.E., Timmerman L.A., Cyster J.G., Thomas M.L., Crabtree G.R., Lewis R.S., Goodnow C.C. Different nuclear signals are activated by the B cell receptor during positive versus negative signaling. Immunity. 6:1997;419-428
79. Hertz M., Nemazee D. BCR ligation induces receptor editing in IgM+IgD- bone marrow B cells in vitro. Immunity. 6:1997;429-436
80. Hibbs M.L., Tarlinton D.M., Armes J., Grail D., Hodgson G., Maglitto R., Stacker S.A., Dunn A.R. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell. 83:1995;301-311
81. Hippen K.L., Buhl A.M., D'Ambrosio D., Nakamura K., Persin C., Cambier J.C. Fc gammaRIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+ mobilization is integrated by CD19 dephosphorylation. Immunity. 7:1997;49-58
82. Ho L.H., Uehara T., Chen C.C., Kubagawa H., Cooper M.D. Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B. Proc. Natl. Acad. Sci. U.S.A. 96:1999;15086-15090
83. Hoffmann R., Seidl T., Neeb M., Rolink A., Melchers F. Changes in gene expression profiles in developing B cells of murine bone marrow. Genome Res. 12:2002;98-111
84. Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 17:1998;1371-1384
85. Ingham R.J., Holgado-Madruga M., Siu C., Wong A.J., Gold M.R. The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor. J. Biol. Chem. 273:1998;30630-30637
86. Ishiai M., Kurosaki M., Pappu R., Okawa K., Ronko I., Fu C., Shibata M., Iwamatsu A., Chan A.C., Kurosaki T. BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. Immunity. 10:1999;117-125
87. Jacob A., Cooney D., Pradhan M., Coggeshall K.M. Convergence of signaling pathways on the activation of ERK in B cells. J. Biol. Chem. 277:2002;23420-23426
88. Jiang A., Craxton A., Kurosaki T., Clark E.A. 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. 188:1998;1297-1306
89. Johnson G.L., Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:2002;1911-1912
90. Johnson S.A., Pleiman C.M., Pao L., Schneringer J., Hippen K., Cambier J.C. Phosphorylated immunoreceptor signaling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases. J. Immunol. 155:1995;4596-4603
91. Jumaa H., Wollscheid B., Mitterer M., Wienands J., Reth M., Nielsen P.J. Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65. Immunity. 11:1999;547-554
92. Jun J.E., Wilson L.E., Vinuesa C.G., Lesage S., Blery M., Miosge L.A., Cook M.C., Kucharska E.M., Hara H., Penninger J.M., Domashenz H., Hong N.A., Glynne R.J., Nelms K.A., Goodnow C.C. Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity. 18:2003;751-762
93. Justement L.B. The role of the protein tyrosine phosphatase CD45 in regulation of B lymphocyte activation. Int. Rev. Immunol. 20:2001;713-738
94. Justement L.B., Campbell K.S., Chien N.C., Cambier J.C. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. Science. 252:1991;1839-1842
95. Kabak S., Skaggs B.J., Gold M.R., Affolter M., West K.L., Foster M.S., Siemasko K., Chan A.C., Aebersold R., Clark M.R. The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways. Mol. Cell. Biol. 22:2002;2524-2535
96. Kane L.P., Shapiro V.S., Stokoe D., Weiss A. Induction of NF-kappaB by the Akt/PKB kinase. Curr. Biol. 9:1999;601-604
97. Kawabuchi M., Satomi Y., Takao T., Shimonishi Y., Nada S., Nagai K., Tarakhovsky A., Okada M. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature. 404:2000;999-1003
98. Kelm S., Gerlach J., Brossmer R., Danzer C.P., 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. 195:2002;1207-1213
99. Khan W.N., Sideras P., Rosen F.S., Alt F.W. The role of Bruton's tyrosine kinase in B-cell development and function in mice and man. Ann. N. Y. Acad. Sci. 764:1995;27-38
100. Kim T.J., Kim Y.T., Pillai S. Association of activated phosphatidylinositol 3-kinase with p120cbl in antigen receptor-ligated B cells. J. Biol. Chem. 270:1995;27504-27509
101. King L.B., Monroe J.G. Immunobiology of the immature B cell: plasticity in the B-cell antigen receptor-induced response fine tunes negative selection. Immunol. Rev. 176:2000;86-104
102. Kitamura D., Kudo A., Schaal S., Muller W., Melchers F., Rajewsky K. A critical role of lambda 5 protein in B cell development. Cell. 69:1992;823-831
103. Kitamura D., Roes J., Kuhn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 350:1991;423-426
104. Kops G.J., de Ruiter N.D., De Vries-Smits A.M., Powell D.R., Bos J.L., Burgering B.M. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature. 398:1999;630-634
105. Kraus M., Pao L.I., Reichlin A., Hu Y., Canono B., Cambier J.C., Nussenzweig M.C., Rajewsky K. Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igbeta cytoplasmic tail. J. Exp. Med. 194:2001;455-469
106. Kraus M., Saijo K., Torres R.M., Rajewsky K. Ig-alpha cytoplasmic truncation renders immature B cells more sensitive to antigen contact. Immunity. 11:1999;537-545
107. Kubagawa H., Burrows P.D., Cooper M.D. A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells. Proc. Natl. Acad. Sci. U.S.A. 94:1997;5261-5266
108. Kubagawa H., Chen C.C., Ho L.H., Shimada T.S., Gartland L., Mashburn C., Uehara T., Ravetch J.V., Cooper M.D. Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B. J. Exp. Med. 189:1999;309-318
109. Kurosaki T. Genetic analysis of B cell antigen receptor signaling. Annu. Rev. Immunol. 17:1999;555-592
110. Kurosaki T. Regulation of B-cell signal transduction by adaptor proteins. Nat. Rev. Immunol. 2:2002;354-363
111. Kurosaki T., Tsukada S. BLNK: connecting Syk and Btk to calcium signals. Immunity. 12:2000;1-5
112. Lam K.P., Kuhn R., Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell. 90:1997;1073-1083
113. Lam K.P., Rajewsky K. B cell antigen receptor specificity and surface density together determine B-1 versus B-2 cell development. J. Exp. Med. 190:1999;471-477
114. Lanoue A., Batista F.D., Stewart M., Neuberger M.S. Interaction of CD22 with alpha2, 6-linked sialoglycoconjugates: innate recognition of self to dampen B cell autoreactivity? Eur. J. Immunol. 32:2002;348-355
115. Lee J.R., Koretzky G.A. Extracellular signal-regulated kinase-2, but not c-Jun NH2-terminal kinase, activation correlates with surface IgM-mediated apoptosis in the WEHI 231 B cell line. J. Immunol. 161:1998;1637-1644
116. Leo A., Schraven B. Adapters in lymphocyte signalling. Curr. Opin. Immunol. 13:2001;307-316
117. Maeda A., Kurosaki M., Kurosaki T. Paired immunoglobulin-like receptor (PIR)-A is involved in activating mast cells through its association with Fc receptor gamma chain. J. Exp. Med. 188:1998;991-995
118. Maeda A., Scharenberg A.M., Tsukada S., Bolen J.B., Kinet J.P., Kurosaki T. Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1. Oncogene. 18:1999;2291-2297
119. Majeti R., Xu Z., Parslow T.G., Olson J.L., Daikh D.I., Killeen N., Weiss A. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell. 103:2000;1059-1070
120. Mecklenbrauker I., Saijo K., Zheng N.Y., Leitges M., Tarakhovsky A. Protein kinase Cdelta controls self-antigen-induced B-cell tolerance. Nature. 416:2002;860-865
121. Meier R., Alessi D.R., Cron P., Andjelkovic M., Hemmings B.A. Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta. J. Biol. Chem. 272:1997;30491-30497
122. Metcalf E.S., Klinman N.R. In vitro tolerance induction of neonatal murine B cells. J. Exp. Med. 143:1976;1327-1340
123. Mizuno K., Tagawa Y., Mitomo K., Arimura Y., Hatano N., Katagiri T., Ogimoto M., Yakura H. 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. 165:2000;1344-1351
124. Murakami M., Nakajima K., Yamazaki K., Muraguchi T., Serikawa T., Honjo T. Effects of breeding environments on generation and activation of autoreactive B-1 cells in anti-red blood cell autoantibody transgenic mice. J. Exp. Med. 185:1997;791-794
125. Nagai K., Takata M., Yamamura H., Kurosaki T. Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling. J. Biol. Chem. 270:1995;6824-6829
126. Nakamura K., Brauweiler A., Cambier J.C. Effects of Src homology domain 2 (SH2)-containing inositol phosphatase (SHIP), SH2-containing phosphotyrosine phosphatase (SHP)-1, and SHP-2 SH2 decoy proteins on Fc gamma RIIB1-effector interactions and inhibitory functions. J. Immunol. 164:2000;631-638
127. Niiro H., Maeda A., Kurosaki T., Clark E.A. The B lymphocyte adaptor molecule of 32 kD (Bam32) regulates B cell antigen receptor signaling and cell survival. J. Exp. Med. 195:2002;143-149
128. Nishizumi H., Horikawa K., Mlinaric-Rascan I., Yamamoto T. A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals. J. Exp. Med. 187:1998;1343-1348
129. Nishizumi H., Taniuchi I., Yamanashi Y., Kitamura D., Ilic D., Mori S., Watanabe T., Yamamoto T. Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice. Immunity. 3:1995;549-560
130. Nitschke L., Carsetti R., Ocker B., Kohler G., Lamers M.C. CD22 is a negative regulator of B-cell receptor signalling. Curr. Biol. 7:1997;133-143
131. Nitschke L., Floyd H., Crocker P.R. New functions for the sialic acid-binding adhesion molecule CD22, a member of the growing family of Siglecs. Scand. J. Immunol. 53:2001;227-234
132. Norvell A., Mandik L., Monroe J.G. Engagement of the antigen-receptor on immature murine B lymphocytes results in death by apoptosis. J. Immunol. 154:1995;4404-4413
133. 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. 13:2000;817-827
134. Otipoby K.L., Andersson K.B., Draves K.E., Klaus S.J., Farr A.G., Kerner J.D., Perlmutter R.M., Law C.L., Clark E.A. CD22 regulates thymus-independent responses and the lifespan of B cells. Nature. 384:1996;634-637
135. Pao L.I., Bedzyk W.D., Persin C., Cambier J.C. Molecular targets of CD45 in B cell antigen receptor signal transduction. J. Immunol. 158:1997;1116-1124
136. Pao L.I., Famiglietti S.J., Cambier J.C. Asymmetrical phosphorylation and function of immunoreceptor tyrosine-based activation motif tyrosines in B cell antigen receptor signal transduction. J. Immunol. 160:1998;3305-3314
137. Papavasiliou F., Jankovic M., Suh H., Nussenzweig M.C. The cytoplasmic domains of immunoglobulin (Ig) alpha and Ig beta can independently induce the precursor B cell transition and allelic exclusion. J. Exp. Med. 182:1995;1389-1394
138. Parent B.A., Wang X., Song W. Stability of the B cell antigen receptor modulates its signaling and antigen-targeting functions. Eur. J. Immunol. 32:2002;1839-1846
139. Pelanda R., Schaal S., Torres R.M., Rajewsky K. A prematurely expressed Ig(kappa) transgene, but not V(kappa)J(kappa) gene segment targeted into the Ig(kappa) locus, can rescue B cell development in lambda5-deficient mice. Immunity. 5:1996;229-239
140. Petro J.B., Gerstein R.M., Lowe J., Carter R.S., Shinners N., Khan W.N. Transitional type 1 and 2 B lymphocyte subsets are differentially responsive to antigen receptor signaling. J. Biol. Chem. 277:2002;48009-48019
141. Plas D.R., Thompson C.B. Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J. Biol. Chem. 278:2003;12361-12366
142. Pleiman C.M., Abrams C., Gauen L.T., Bedzyk W., Jongstra J., Shaw A.S., Cambier J.C. Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and phosphorylated Ig-alpha. Proc. Natl. Acad. Sci. U.S.A. 91:1994a;4268-4272
143. Pleiman C.M., Hertz W.M., Cambier J.C. Activation of phosphatidylinositol-3′ kinase by Src-family kinase SH3 binding to the p85 subunit. Science. 263:1994b;1609-1612
144. Qian Y., Santiago C., Borrero M., Tedder T.F., Clarke S.H. Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds. J. Immunol. 166:2001;2412-2419
145. Rawlings D.J. Bruton's tyrosine kinase controls a sustained calcium signal essential for B lineage development and function. Clin. Immunol. 91:1999;243-253
146. Rawlings D.J., Saffran D.C., Tsukada S., Largaespada D.A., Grimaldi J.C., Cohen L., Mohr R.N., Bazan J.F., Howard M., Copeland N.G., et al. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science. 261:1993;358-361
147. Reichlin A., Hu Y., Meffre E., Nagaoka H., Gong S., Kraus M., Rajewsky K., Nussenzweig M.C. B cell development is arrested at the immature B cell stage in mice carrying a mutation in the cytoplasmic domain of immunoglobulin beta. J. Exp. Med. 193:2001;13-23
148. Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J. Biol. Chem. 274:1999;17179-17183
149. Reth M. Antigen receptor tail clue. Nature. 338:1989;383-384
150. Richards J.D., Dave S.H., Chou C.H., Mamchak A.A., DeFranco A.L. Inhibition of the MEK/ERK signaling pathway blocks a subset of B cell responses to antigen. J. Immunol. 166:2001;3855-3864
151. Richards J.D., Gold M.R., Hourihane S.L., DeFranco A.L., Matsuuchi L. Reconstitution of B cell antigen receptor-induced signaling events in a nonlymphoid cell line by expressing the Syk protein-tyrosine kinase. J. Biol. Chem. 271:1996;6458-6466
152. Rickert R.C., Rajewsky K., Roes J. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature. 376:1995;352-355
153. Rossbacher J., Shlomchik M.J. The B cell receptor itself can activate complement to provide the complement receptor 1/2 ligand required to enhance B cell immune responses in vivo. J. Exp. Med. 198:2003;591-602
154. Rowley R.B., Burkhardt A.L., Chao H.G., Matsueda G.R., Bolen J.B. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J. Biol. Chem. 270:1995;11590-11594
155. Rui L., Vinuesa C.G., Blasioli J., Goodnow C.C. Resistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling. Nat. Immunol. 4:2003;594-600
156. Ruland J., Mak T.W. Transducing signals from antigen receptors to nuclear factor kappaB. Immunol. Rev. 193:2003;93-100
157. Russell D.M., Dembic Z., Morahan G., Miller J.F., Burki K., Nemazee D. Peripheral deletion of self-reactive B cells. Nature. 354:1991;308-311
158. Saijo K., Mecklenbrauker I., Santana A., Leitger M., Schmedt C., Tarakhovsky A. Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha. J. Exp. Med. 195:2002;1647-1652
159. Saijo K., Schmedt C., Su I.H., Karasuyama H., Lowell C.A., Reth M., Adachi T., Patke A., Santana A., Tarakhovsky A. Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development. Nat. Immunol. 4:2003;274-279
160. Saito K., Scharenberg A.M., Kinet J.P. Interaction between the Btk PH domain and phosphatidylinositol-3, 4, 5-trisphosphate directly regulates Btk. J. Biol. Chem. 276:2001;16201-16206
161. Sanchez M., Misulovin Z., Burkhardt A.L., Mahajan S., Costa T., Franke R., Bolen J.B., Nussenzweig M. Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta. J. Exp. Med. 178:1993;1049-1055
162. Sandel P.C., Monroe J.G. Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter. Immunity. 10:1999;289-299
163. Sato S., Steeber D.A., Tedder T.F. The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation. Proc. Natl. Acad. Sci. U.S.A. 92:1995;11558-11562
164. Scharenberg A.M., El-Hillal O., Fruman D.A., Beitz L.O., Li Z., Lin S., Gout I., Cantley L.C., Rawlings D.J., Kinet J.P. 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. 17:1998;1961-1972
165. Shoham T., Rajapaksa R., Boucheix C., Rubinstein E., Poe J.C., Tedder T.F., Levy S. The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment. J. Immunol. 171:2003;4062-4072
166. Spanopoulou E., Roman C.A., Corcoran L.M., Schlissel M.S., Silver D.P., Nemazee D., Nussenzweig M.C., Shinton S.A., Hardy R.R., Baltimore D. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 8:1994;1030-1042
167. Sproul T.W., Malapati S., Kim J., Pierce S.K. Cutting edge: B cell antigen receptor signaling occurs outside lipid rafts in immature B cells. J. Immunol. 165:2000;6020-6023
168. Suzuki H., Terauchi Y., Fujiwara M., Aizawa S., Yazaki Y., Kadowaki T., Koyasu S. Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase. Science. 283:1999;390-392
169. Takata M., Kurosaki T. A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2. J. Exp. Med. 184:1996;31-40
170. Takata M., Sabe H., Hata A., Inazu T., Homma Y., Nukada T., Yamamura H., Kurosaki T. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways. EMBO J. 13:1994;1341-1349
171. Tamir I., Dal Porto J.M., Cambier J.C. Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction. Curr. Opin. Immunol. 12:2000;307-315
172. Tiegs S.L., Russell D.M., Nemazee D. Receptor editing in self-reactive bone marrow B cells. J. Exp. Med. 177:1993;1009-1020
173. Toker A., Cantley L.C. Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature. 387:1997;673-676
174. Torres R.M., Hafen K. A negative regulatory role for Ig-alpha during B cell development. Immunity. 11:1999;527-536
175. Trushin S.A., Pennington K.N., Algeciras-Schimnich A., Paya C.V. Protein kinase C and calcineurin synergize to activate IkappaB kinase and NF-kappaB in T lymphocytes. J. Biol. Chem. 274:1999;22923-22931
176. Tsitsikov E.N., Gutierrez-Ramos J.C., Geha R.S. Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 94:1997;10844-10849
177. Tsukada S., Saffran D.C., Rawlings D.J., Parolini O., Allen R.C., Klisak I., Sparkes R.S., Kubagawa H., Mohandas T., Quan S., et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 72:1993;279-290
178. Turner M., Mee P.J., Costello P.S., Williams O., Price A.A., Duddy L.P., Furlong M.T., Geahlen R.L., Tybulewicz V.L. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature. 378:1995;298-302
179. Tuveson D.A., Carter R.H., Soltoff S.P., Fearon D.T. CD19 of B cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science. 260:1993;986-989
180. Vilen B.J., Burke K.M., Sleater M., Cambier J.C. Transmodulation of BCR signaling by transduction-incompetent antigen receptors: implications for impaired signaling in anergic B cells. J. Immunol. 168:2002;4344-4351
181. Vilen B.J., Nakamura T., Cambier J.C. Antigen-stimulated dissociation of BCR mIg from Ig-alpha/Ig-beta: implications for receptor desensitization. Immunity. 10:1999;239-248
182. Vorechovsky I., Vihinen M., de Saint Basile G., Honsova S., Hammarstrom L., Muller S., Nilsson L., Fischer A., Smith C.I. DNA-based mutation analysis of Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinaemia. Hum. Mol. Genet. 4:1995;51-58
183. Wakabayashi C., Adachi T., Wienands J., Tsubata T. A distinct signaling pathway used by the IgG-containing B cell antigen receptor. Science. 298:2002;2392-2395
184. Wang Y., Brooks S.R., Li X., Anzelon A.N., Rickert R.C., Carter R.H. The physiologic role of CD19 cytoplasmic tyrosines. Immunity. 17:2002;501-514
185. Wechsler R.J., Monroe J.G. Immature B lymphocytes are deficient in expression of the src-family kinases p59fyn and p55fgr1. J. Immunol. 154:1995;1919-1929
186. Wienands J., Schweikert J., Wollscheid B., Jumaa H., Nielsen P.J., Reth M. SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J. Exp. Med. 188:1998;791-795
187. Wong S.C., Chew W.K., Tan J.E., Melendez A.J., Francis F., Lam K.P. Peritoneal CD5+ B-1 cells have signaling properties similar to tolerant B cells. J. Biol. Chem. 277:2002;30707-30715
188. Wu Y., Nadler M.J., Brennan L.A., Gish G.D., Timms J.F., Fusaki N., Jongstra-Bilen J., Tada N., Pawson T., Wither J., Neel B.G., Hozumi N. The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1. Curr. Biol. 8:1998;1009-1017
189. Yokozeki T., Adler K., Lankar D., Bonnerot C. B cell receptor-mediated Syk-independent activation of phosphatidylinositol 3-kinase, Ras, and mitogen-activated protein kinase pathways. J. Immunol. 171:2003;1328-1335
190. Yotsumoto K., Okoshi Y., Shibuya K., Yamazaki S., Tahara-Hanaoka S., Honda S., Osawa M., Kuroiwa A., Matsuda Y., Tenen D.G., Iwama A., Nakauchi H., Shibuya A. Paired activating and inhibitory immunoglobulin-like receptors, MAIR-I and MAIR-II, regulate mast cell and macrophage activation. J. Exp. Med. 198:2003;223-233
191. Young F., Ardman B., Shinkai Y., Lansford R., Blackwell T.K., Mendelsohn M., Rolink A., Melchers F., Alt F.W. Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation. Genes Dev. 8:1994;1043-1057
192. Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 92:1998;83-92