Proximal B cell receptor signaling pathways

Engagement of the B cell antigen receptor by antigen initiates a complex and interconnected cascade of signaling pathways that determine whether a B cell will divide, differentiate, or die. Both biochemical and genetic studies have defined the principal molecules, including the BCR components Igσ and Igβ, Src kinases, Syk, and Btk. Linker proteins such as BLNK have recently been shown to play a vital role in organizing proximal signaling molecules and coupling the BCR to distal signaling pathways. In this review, we will pay particular attention to how BCR-proximal kinases coordinate the activation of PLCγ2, leading to the initiation and amplification of BCR-mediated calcium flux and the activation of PI-3 kinase.