The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases

Christian M. Karsten, Jörg Köhl*

*Corresponding author for this work
71 Citations (Scopus)


Immunoglobulin G (IgG)-mediated activation of complement and IgG Fc receptors (FcγRs) are important defense mechanisms of the innate immune system to ward off infections. However, the same mechanisms can drive severe and harmful inflammation, when IgG antibodies react with self-antigens in solution or tissues, as described for several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and immune vasculitis. More specifically, IgG immune complexes (ICs) can activate all three pathways of the complement system resulting in the generation of C3 and C5 cleavage products that can activate a panel of different complement receptors on innate and adaptive immune cells. Importantly, complement and FcγRs are often co-expressed on inflammatory immune cells such as neutrophils, monocytes, macrophages or dendritic cells and act in concert to mediate the inflammatory response in autoimmune diseases. In this context, the cross-talk between the receptor for the anaphylatoxin C5a, i.e. C5ar1 (CD88) and FcγRs is of major importance. Recent data suggest a model of bidirectional regulation, in which CD88 acts upstream of FcγRs and sets the threshold for FcγR-dependent effector responses by regulating the ratio between activating and inhibitory FcγRs. Vice versa, FcγR ligation can either amplify or block C5aR-mediated effector functions, depending on whether IgG IC aggregate activating or inhibitory FcγRs. Further, complement and FcγRs cooperate on B cells and on follicular dendritic cells to regulate the development of autoreactive B cells, their differentiation into plasma cells and, eventually, the production of autoantibodies. Here, we will give an update on recent findings regarding this complex regulatory network between complement and FcγRs, which may also regulate the inflammatory response in allergy, cancer and infection.

Original languageEnglish
Issue number11
Pages (from-to)1067-1079
Number of pages13
Publication statusPublished - 01.01.2012


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