BCR signaling pathway

B cell antigen receptor (BCR) is a multiprotein complex expressed on the surface of B cells which consists of a ligand binding moiety, the antigen-binding transmembrane immunoglobulin (mIg), paired with the signal transduction moiety, Ig-α/Ig-βheterodimers(CD79a/CD79b). The BCR signaling pathway is crucial for proper B-cell development, activation, proliferation, differentiation and consequently for humoral immune response. Engagement of the BCR by antigen induces membrane movement and aggregation of BCR components that lead to phosphorylation of ITAMs in the cytoplasmic tails of CD79a and CD79b. The latter is accomplished by the SRC family kinase LYN. The phosphorylated ITAMs recruit the spleen tyrosine kinase (SYK) to the receptor, where it becomes activated by phosphorylation of tyrosines, and propagates the signal activation to downstream signaling proteins. Activation of SYK plays a critical role in BCR signaling, initiating the formation of the BCR signalosome, the adaptor proteins, such as CD19 and B-cell linker (BLNK), and Bruton's tyrosine kinases (BTK), and signaling enzymes such as PLCγ2, PI3K, and Vav. Signals emanating from those signalosomes initiate and regulate downstream signaling systems including RAS/RAF/MEK/ERK pathway, which are significant for B-cell fate decisions such as proliferation, survival, differentiation and cell death.

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