THE ROLE OF COMPLEMENT AND COMPLEMENT RECEPTORS IN INDUCTION AND REGULATION OF IMMUNITY

Covalent attachment of activated complement C3 (C3d) to antigen links innate and adaptive immunity by targeting antigen to follicular dendri tic cells (FDC) and B cells via specific receptors CD21 and CD35. Rece nt characterization of knockout mice deficient in complement component s C3, C4, or the receptors CD21 and CD35 as well as biochemical studie s of the CD21/CD19/Tapa-1 coreceptor on B cells have helped to elucida te the mechanism of complement regulation of both B-l and B-2 lymphocy tes. Interestingly, natural antibody of the adaptive immune system pro vides a major recognition role in activation of the complement system, which in turn enhances activation of antigen-specific B cells. Enhanc ement of the primary and secondary immune response to T-dependent anti gens is mediated by coligation of the coreceptor and the B cell antige n receptor, which dramatically increases follicular retention and B ce ll survival within the germinal center. Most recent evidence suggests that complement also regulates elimination of self-reactive B cells, a s breeding of mice that are deficient in C4 or CD21/CD35 with the lupu s-prone strain of lpr mice demonstrates an exacerbation of disease due to an increase in autoantibodies.