Regulation of Human B-Cell Activation and Adhesion

Human B lymphocyte differentiation is regulated by signals transmitted after binding of cytokines to their specific receptors and/or cross-linking of cell-cell adhesion receptors. In addition to surface immunoglobulin (sIg) receptors for antigen, a number of B cell-associated surface molecules have now been identified which may regulate activation and adhesion of B cells. These include members of the Ig supergene family such as CD19, CD22, B7/BB1, and BMC1, cell surface enzymes such as CD10, CD73, and CDw75, and proteins with multiple transmembrane domains such as CD20 and CD37. In this review we describe how several of these accessory molecules may affect signaling via antigen receptors and influence primary vs secondary immune responses. For instance, signaling via either CD21 or CD22 can augment responses to anti-Ig; the B cell activation marker B7/BB1 may function to trigger T cells via its ligand, CD28, to produce cytokines which in turn stimulate B cells; and the receptor, CD40, may transmit a signal to protect germinal center B cells from undergoing programmed cell death. Understanding how B cell accessory molecules regulate key interconnections during development may provide insights into the control and management of diseases with B-cell dysfunctions.