Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex

Complement is an essential innate immune mechanism that recognizes and eradicates microbes and associated toxins. In addition, complement receptors (CD21 and CD35) on B cells cooperate with the B-cell antigen receptor (BCR) to efficiently recognize and respond to antigens bearing complement C3d(g). Fixation of C3d(g) to antigen confers adjuvant properties and therefore its deposition may need to be carefully regulated to avoid autoreactivity. CD21 and/or CD35 engagement is nonmitogenic, and B-cell activation via BCR–CD21 coligation is enhanced through the recruitment of CD19. Recent efforts have sought a better understanding of the topological and biochemical properties of BCR and coreceptor (CD19–CD21–CD81) signaling, as well as the context for complement activation in the response to foreign and self antigens.