B Cell Receptor Signaling

Signaling through the B cell receptor (BCR) plays a critical role at multiple checkpoints of B cell biology. BCR acts as a gatekeeper of the progression of their early development in bone marrow (BM). It is also essential in triggering mechanisms such as clonal deletion and receptor editing to eliminate autoreactive B cells. In the periphery, it most importantly functions as a receptor that recognizes various extracellular antigens in response to bacterial and viral infections for conferring host defense. The recognition of antigens by BCR is the first step to receive T cell help for the functional differentiation of naive B cells toward plasma cells, germinal center (GC) B cells and memory B cells. In addition, similar to the role of BCR in the early stages of B cell development, BCR signaling plays a crucial role in the prevention of dysregulated activation of autoreactive B cells which can induce autoimmunity in the secondary lymphoid organs. Thus, since BCR is essential for the proper elicitation of immune responses by B cells, signaling through the BCR is tightly controlled by the intracellular positive and negative regulators. In this chapter, the mechanisms of activation and repression of BCR signaling are reviewed on the basis of the recent findings.