CORECEPTOR AND ACCESSORY REGULATION OF B-CELL ANTIGEN RECEPTOR SIGNAL-TRANSDUCTION

The development and function of the immune system is precisely regulat ed to assure the generation of protective immune responses while avoid ing autoimmunity. This regulation is accomplished by the engagement of a multitude of cell-surface receptors which transduce signals that ac tivate or regulate cell differentiative and proliferative pathways. In some cases biologic responses reflect the integration of signals gene rated by co-aggregation of multiple receptors by complex ligands. For example, B-cell responses to antigen receptor aggregation can be modul ated by co-aggregation of receptors for immunoglobulin G (Fc gamma RII B1), complement components (CR2), and alpha 2,6-sialoglycoproteins (CD 22). Here we review our recent studies of molecular mechanisms underly ing co-recepcor modulation of B-cell antigen receptor signaling. Our r esults define interesting circuitry involving interactions among the B -cen 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.