Co-receptor and accessory regulation of B-cell antigen receptor signal transduction

Summary: The development and function of the immune system is precisely regulated to assure the generation of protective immune responses while avoiding autoimmunity. This regulation is accomplished by the engagement of a multitude of cell-surface receptors which transduce signals that activate or regulate cell differentiative and proliferative pathways. In some cases biologic responses reflect the integration of signals generated by co-aggregation of multiple receptors by complex ligands. For example, B-cell responses to antigen receptor aggregation can be modulated by co-aggregation of receptors for immunoglobulin G (FcγRIIB1), complement components (CR2). and 4aL2,6-sialoglycoproteins (CD22). Here we review our recent studies of molecular mechanisms underlying co-receptor modulation of B-cell antigen receptor signaling. Our results define interesting circuitry involving interactions among the B-cell antigen receptor, CD 19 and FcγRIIB1. CD 19 may function as an important integrator of positive and negative signals that regulate B-cell antigen receptor signal output.