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

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 (Fc gamma RIIB1), complement components (CR2), and alpha 2, 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, CD19 and Fc gamma RIIB1. CD19 may function as an important integrator of positive and negative signals that regulate B-cell antigen receptor signal output.