Fc gamma receptor

The FcγR family recognizes the Fc part of IgG and is divided into several main classes (FcγRI, FcγRII, and FcγRIII), consisting of activating and inhibitory receptors, which additionally differ in their affinities to IgG and are specific for the individual IgG subclasses.

Fc receptors are predominantly membrane-bound receptors for different immunoglobulin isotypes. All molecules except the FcRn receptor belong to the immunoglobulin superfamily (see FC receptors below). The name is based on the binding specificity of the receptors to a part of the C-terminus of an antibody (called Fc fragment crystallizable) and the constant region of an antibody. Fc receptors are glycosylated. They are found on the surface of phagocytes, B lymphocytes, NK cells and dendritic cells.

The biological activity of an IgG antibody (e.g. neutralization of viruses and bacterial toxins, mediation of an anti-tumour response) is determined by the relative affinity to the respective antigen and to the respective FcγR. Certain receptor variants (e.g. the high-affinity Val158-FcγRIIIa receptor variant) have been shown to respond better to rituximab antibody therapy in rheumatoid arthritis than other receptor variants (Ruyssen-Witrand A et al. 2012).

Several isoforms have been identified within each FcγR class. The low-affinity FcγRII and FcγRIII act as receptors for antigen-antibody complexes (immune complexes; IC), while FcγRI and the FcγRIV identified in mice also bind monomeric IgG as high-affinity receptors (Bruhns P 2012).

Defects in the functioning of the FcγR system can contribute to inflammatory autoimmune processes and impaired immune defense (Schmidt RE et al. 2005). A distinction is made between different structural types of the Fcγ receptor

• FcγRI or CD64 with the subdivision into Fcγ receptor Ia, Fcγ receptor Ib and Fcγ receptor Ic (syn. CD64a, CD64b and CD64c).
• FcγRII or CD32 (Fcγ receptor IIa (synonym CD32a), Fcγ receptor IIb (synonym CD32b), Fcγ receptor IIc
• Fcγ receptor III / FcγRIII (syn. CD16) with further subdivision into: Fcγ-IIIa (synonym CD16a) and Fcγ receptor IIIb (synonym CD16b).

The majority of FcγR (FcγRIa, and IIIa) are multimeric receptors that mediate a variety of immunological defense reactions via the ITAM ("immunoreceptor tyrosine activation motif") signal sequence of the common FcRγ chain, such as antibody-dependent cytotoxicity (ADCC), phagocytosis of pathogenic germs, enhancement of antigen presentation and the release of inflammatory mediators.

The FcγRII receptors are monomeric receptors that perform opposing inhibitory functions due to different structural motifs. Thus, the expression of FcγRIIb on follicular B cells and plasma cells is important for the maintenance of peripheral tolerance and the regulation of antibody production.

The FcγR family recognizes the Fc part of IgG and is divided into several main classes (FcγRI, FcγRII, and FcγRIII), consisting of activating and inhibitory receptors, which additionally differ in their affinities to IgG and are specific for the individual IgG subclasses.

1. Bruhns P (2012) Properties of mouse and human IgG receptors and their contribution to disease models. Blood 119:5640-5649)
2. Gessner JE et al (2013) Fcγ receptors [Fcγ receptors]. Z Rheumatol 72:68-70.
3. Schmidt RE et al. (2005) Fc receptors and their interaction with complement in autoimmunity. Immunol Lett 100:56-67).
4. Ruyssen-Witrand A et al. (2012) Fc gamma receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis 71:875-877)