FcγRIIB and autoimmunity

Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fc gamma receptors (Fc gamma Rs). The inhibitory receptor Fc gamma RIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in Fc gamma RIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which Fc gamma RIIB controls the adaptive immune response have been described. Notably, Fc gamma RIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of Fc gamma RIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of Fc gamma RIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity.