Molecular dissection of B cell antigen receptor signaling (review)

In B lymphocytes, signaling through the B cell antigen receptor (BCR) contributes to cell fate decisions with different extents of receptor engagement leading to such outcomes as cell death, survival, or proliferation. During the past several years we have seen significant strides in our understanding of the signaling pathways that connect the BCR to the nucleus. Stimulation of the BCR leads to the activation of three types of intracellular protein tyrosine kinases Lyn, Syk, and Btk. Concerted action of these tyrosine kinases leads to the phosphorylation of multiple substrates and to activation of a variety of signaling pathways including phospholipase C-gamma, Ras, and phosphatidylinositol 3-kinase activation. The ability of B lymphocytes to react appropriately to a wide variety of environment stimuli requires a high degree of regulation on these multiple signaling pathways.