Fc Receptors


Receptors for the Fc region of immunoglobulins (Igs) play a central role during an immune response as they link humoral responses to cellular activities. The majority of these leucocyte Fc receptors exist as heterooligomeric complexes with unique ligand‐binding α chains and promiscuous accessory subunits involved in intracellular signal transduction. In humans, five major Fc receptor classes are known, FcγR for IgG, FcαR for IgA, FcɛR for IgE, FcμR for IgM and FcδR for IgD. Integration of both activating and inhibitory signals occurs on Ig‐Fc engagement of Fc receptors. Given their vital role in maintaining balanced immunity, dysregulation of Fc receptor function may lead to inflammatory or autoimmune disease. As such, much effort is focussed on identifying which single nucleotide polymorphisms and copy number variations in Fc receptor genes are linked with disease and understanding of how these affect therapeutic options.

Key Concepts:

  • Fc receptors link the humoral and cellular arms of the immune system.

  • Cellular activities may be triggered by Fc receptor α chains independent of FcR γ chains.

  • Fc receptor ITAM and ITIM motifs transmit opposite signals to control leucocyte activation.

  • Inside‐out regulation of Fc receptors influences their affinity for immunoglobulin ligands.

  • Fc receptor genetic variations are linked with inflammation, autoimmunity and cancer.

Keywords: Fc receptors; CD64; CD32; CD16; CD89

Figure 1.

Schematic representation of human Fc receptors. The extracellular parts of most human Fc receptors are composed of varying amounts (1–5) of immunoglobulin domains. The two exceptions are the lectin family member FcɛRII and the major histocompatibility complex (MHC) class I protein family member FcRn. Based on their function FcRs can mediate activating signals via ITAM (green box) which consist of YxxLxxxxxxxYxxL (Y=tyrosine, L=leucine, X=any amino acid). The ITAM can either be located on the intracellular part of the receptors (FcγRIIa and FcγRIIc) or on the associated γ chain (FcγRI, FcγRIIIa, FcɛRI and FcαRI). Next to its role in signalling, the γ chain (in blue) is also essential for surface expression. The sole inhibiting FcR, FcγRIIb, bears an ITIM (red box) on its intracellular tail, which consists of Y/V/L/S/xYxxL/V (Y, tyrosine; V, valine; S, serine; L, leucine and X=any amino acid). FcγRIIIb is a glycosylphosphatidylinositol (GPI)‐linked activating receptor that has no intracellular tail.



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Further Reading

Ivashkiv LB (2011) How ITAMs inhibit signaling. Science Signaling 4(169): pe20.

Niederer HA, Clatworthy MR, Willcocks LC and Smith KG (2010) FcgammaRIIB, FcgammaRIIIB, and systemic lupus erythematosus. Annals of the New York Academy of Sciences 1183: 69–88.

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Jacobino, Shamir, Slomp, Anne, Boross, Peter, and Leusen, Jeanette HW(Mar 2013) Fc Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000916.pub3]