DIVERGENT ROLES FOR FC-RECEPTORS AND COMPLEMENT IN-VIVO

Recent results obtained in mice deficient in either FcRs or complement have revealed distinct functions for these two classes of molecules. While each is capable of interacting with antibodies or immune complex es, the two systems mediate distinct biological effector responses. Co mplement-deficient mice are unable to mediate innate immune responses to several bacterial pathogens and bacterial toxins, yet respond norma lly to the presence of cytotoxic antibodies and pathogenic immune comp lexes. In contrast, FcR-deficient mice display no defects in innate im munity or susceptibility to a variety of pathogens, yet they are unabl e to mediate inflammatory responses to cytotoxic IgG antibodies or IgG immune complexes, despite the presence of a normal complement system. These results lead to the surprising conclusion that these two system s have evolved distinct functions in host immunity, with complement an d its receptors mediating the interaction of natural antibodies (IgM) with pathogens to effect protection, while FcRs couple the interaction of IgG antibodies to effector cells to trigger inflammatory sequelae. These results necessitate a fundamental revision of the role of these antibody-binding systems in the immune response.