B Cell Receptor Signaling
Pathway Description:
The B cell antigen receptor (BCR) is composed of membrane immunoglobulin molecules (mIg) and associated Igα/Igβ (CD79a/CD79b) heterodimers (α/β). The mIg subunits bind antigen resulting in receptor aggregation, while the α/β subunits transduce signals to the cell interior. Receptor aggregation rapidly activates Src family kinases, including Lyn, Blk and Fyn as well as the Syk and Btk tyrosine kinases, initiating complex signaling cascades involving multiple adaptors, kinases, phosphatases, GTPases and transcription factors. The complexity of BCR signaling permits many distinct outcomes, including differentiation, survival, apoptosis, proliferation and tolerance. The outcome of the response is determined by the maturation state of the cell, the nature of the antigen, the magnitude and duration of BCR signaling, and signals from other receptors such as CD40. Many other transmembrane proteins, some of which are receptors, are known to modulate specific elements of BCR signaling. A few of these, including CD45, CD19, CD22, and FcγRIIB1 (CD32), are indicated above in yellow. The magnitude and duration of BCR signaling are limited by negative feedback loops including those involving Cbl, the Lyn/CD22/SHP-1 pathway, FcγRIIB1, and internalization of the BCR. Please refer to the Akt/PKB signaling pathway diagram and the NF-κB signaling pathway diagrams for more details about the activation and functions of these pathways.
Selected Reviews:
- Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J (2004) B cell antigen receptor signaling 101. Mol. Immunol. 41(6-7), 599–613.
- Glynne R, Ghandour G, Rayner J, Mack DH, Goodnow CC (2000) B-lymphocyte quiescence, tolerance and activation as viewed by global gene expression profiling on microarrays. Immunol. Rev. 176, 216–46.
- Gold MR (2002) To make antibodies or not: signaling by the B-cell antigen receptor. Trends Pharmacol. Sci. 23(7), 316–24.
- Kurosaki T (2002) Regulation of B-cell signal transduction by adaptor proteins. Nat. Rev. Immunol. 2(5), 354–63.
- Monroe JG (2006) ITAM-mediated tonic signalling through pre-BCR and BCR complexes. Nat. Rev. Immunol. 6(4), 283–94.
- Niiro H, Clark EA (2002) Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2(12), 945–56.
CST would like to thank Prof. Michael R. Gold, University of British Columbia,Vancouver, British Columbia, for contributing to this diagram.
created November 2002 • revised January 2007
