B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes.

Organismal Systems; Immune system

PMID:12461567

Niiro H, Clark EA.

Regulation of B-cell fate by antigen-receptor signals.

Nat Rev Immunol 2:945-56 (2002)
DOI:10.1038/nri955

PMID:10358768

Kurosaki T.

Genetic analysis of B cell antigen receptor signaling.

Annu Rev Immunol 17:555-92 (1999)
DOI:10.1146/annurev.immunol.17.1.555

PMID:15886119

Nitschke L.

The role of CD22 and other inhibitory co-receptors in B-cell activation.

Curr Opin Immunol 17:290-7 (2005)
DOI:10.1016/j.coi.2005.03.005

PMID:15752555

Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM.

Complement: central to innate immunity and bridging to adaptive responses.

Immunol Lett 97:171-9 (2005)
DOI:10.1016/j.imlet.2004.11.010

PMID:12033741

Kurosaki T.

Regulation of B-cell signal transduction by adaptor proteins.

Nat Rev Immunol 2:354-63 (2002)
DOI:10.1038/nri801

PMID:15364057

Nitschke L, Tsubata T.

Molecular interactions regulate BCR signal inhibition by CD22 and CD72.

Trends Immunol 25:543-50 (2004)
DOI:10.1016/j.it.2004.08.002

PMID:15771577

Jumaa H, Hendriks RW, Reth M.

B cell signaling and tumorigenesis.

Annu Rev Immunol 23:415-45 (2005)
DOI:10.1146/annurev.immunol.23.021704.115606

PMID:15886112

Rickert RC.

Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex.

Curr Opin Immunol 17:237-43 (2005)
DOI:10.1016/j.coi.2005.03.001

PMID:15457440

Zouali M, Sarmay G

B lymphocyte signaling pathways in systemic autoimmunity: implications for pathogenesis and treatment.

Arthritis Rheum 50:2730-41 (2004)
DOI:10.1002/art.20487

PMID:15322145

Chiles TC.

Regulation and function of cyclin D2 in B lymphocyte subsets.

J Immunol 173:2901-7 (2004)
DOI:10.4049/jimmunol.173.5.2901

PMID:15626471

Allam A, Marshall AJ

Role of the adaptor proteins Bam32, TAPP1 and TAPP2 in lymphocyte activation.

Immunol Lett 97:7-17 (2005)
DOI:10.1016/j.imlet.2004.09.019

PMID:12119152

Gold MR

To make antibodies or not: signaling by the B-cell antigen receptor.

Trends Pharmacol Sci 23:316-24 (2002)
DOI:10.1016/S0165-6147(02)02045-X

PMID:9697839

Fu C, Turck CW, Kurosaki T, Chan AC

BLNK: a central linker protein in B cell activation.

Immunity 9:93-103 (1998)
DOI:10.1016/S1074-7613(00)80591-9

PMID:11163197

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 13:817-27 (2000)
DOI:10.1016/S1074-7613(00)00079-0

PMID:18086859

Shinohara H, Maeda S, Watarai H, Kurosaki T

IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells.

J Exp Med 204:3285-93 (2007)
DOI:10.1084/jem.20070379