Signal Transduction by the B Cell Antigen Receptor

Abstract

The production of antibodies is initiated upon recognition of antigen by antigen-specific receptors expressed on the cell surface of B lymphocytes. Furthermore, antigen receptors control the development of immunocompetent B cells to tolerate self-antigens but differentiate rapidly into antibody-secreting plasma cells upon encounter with foreign antigens. Hence, ligation of the B cell antigen receptor (BCR) does not elicit all-or-nothing signals but controls a network of intracellular signaling cascades that can be modified by coreceptors in a developmental stage-specific and antigen-dependent manner. Moreover, the ligated BCR becomes internalized by endocytosis allowing for the processing of captured protein antigens and the subsequent presentation of peptide products on major histocompatibility complex molecules to T helper cells. This article summarizes how the catalytically inert BCR connects to enzymatic activity provided by cytoplasmic protein tyrosine kinases, which in turn orchestrate various downstream effector systems for the generation of second messengers, activation of transcription factors, or targeting of the ligated antigen receptor to vesicular compartments of antigen processing. The structural backbone of these signal chains is provided by catalytically inactive adaptor proteins. Any failure to precisely launch or adjust antigen receptor signals can blunt humoral immune responses or promote the formation of B-lymphoid malignancies.