FcγRII and multi-system autoimmune disease

The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (Fc gamma R) and in particular the most widely expressed of these, Fc gamma RII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation. Studies of the Fc gamma RII include structure/function relationships, investigation of the associations between FcR polymorphisms and human disease and animal studies using knockout or transgenic mouse models. These investigations showed that the various forms of Fc gamma RII interact with immune complexes to either initiate or inhibit inflammation. In conjunction with environmental antigens and genotype, the Fc gamma RII activating and inhibitory receptors determine the nature and magnitude of response to antigens. In this review, the structure and function of the Fc gamma RIIs and their role in immune complex-mediated auto-immunity are discussed.