title: FcγRIIB and autoimmunity.
abstract: 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 Fcγ receptors (FcγRs). The inhibitory receptor FcγRIIB 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 FcγRIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which FcγRIIB controls the adaptive immune response have been described. Notably, FcγRIIB 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 FcγRIIB 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 FcγRIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity.
authors.affiliation: Inserm UMR_S996, LabEx LERMIT, Université Paris-Sud, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Espéli
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.
authors.forename: Menna R
authors.initials: MR
authors.lastname: Clatworthy
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D056747:Immunomodulation; D051379:Mice; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
chemical_list: C499173:FCGR2B protein, human; D017452:Receptors, IgG
keywords: Fcγ receptors; autoantibodies; dendritic cells; germinal center B cells; lymphangiogenesis; macrophages