The BCR (B-Cell antigen Receptor) plays a critical role in development, survival, and activation of B cells. The BCR is composed of mIg molecules (Membrane Immunoglobulin) and associated Ig-Alpha/Ig-Beta heterodimer. The mIg subunits bind antigen and cause receptor aggregation, while the Alpha/Beta subunits transduce signals to the cell interior. Engagement of receptor activates three types of intracellular protein tyrosine kinases, Syk (Spleen Tyrosine Kinase), BTK (Bruton agammaglobulinemia Tyrosine Kinase) and several members of the Src-family of tyrosine kinases (Ref.1). Once activated, these tyrosine kinases phosphorylate signaling components and thereby activate various signaling pathways, including PIP2 (Phosphatidyl Inositol 4,5-Bisphosphate) breakdown, Ras activation, the Vav/Rho family pathway, MAPK (Mitogen-Activated Protein Kinase) pathways and PI3K (Phosphoinositide-3 Kinase) activation (Ref.2).
The complexity of BCR signaling permits many distinct outcomes, including proliferation, differentiation, apoptosis, survival and tolerance. [...]