Many cells feature membrane glycoproteins called Fc receptors (FcR) that have an affinity for the Fc portion of the antibody molecule. These receptors are essential for many of the biological functions of antibodies. Fc receptors are responsible for the movement of antibodies across cell membranes and the transfer of IgG from mother to fetus across the placenta. These receptors also allow passive acquisition of antibody by many cell types, including B and T lymphocytes, neutrophils, mast cells, eosinophils, macrophages, and natural killer cells. Consequently, Fc receptors provide a means by which antibodies—the products of the adaptive immune system—can recruit such key cellular elements of innate immunity as macrophages and natural killer cells. Engagement of antibody-bound antigens by the Fc receptors of macrophages or neutrophils provides an effective signal for the efficient phagocytosis (opsonization) of antigen-antibody complexes. In addition to triggering such effector functions as opsonization or ADCC, crosslinking of Fc receptors by antigen-mediated crosslinking of FcR-bound antibodies can generate immunoregulatory signals that affect cell activation, induce differentiation and, in some cases, downregulate cellular responses.
There are many different Fc receptors (Figure 4-19). The poly Ig receptor is essential for the transport of polymeric immunoglobulins (polymeric IgA and to some extent, pen-tameric IgM) across epithelial surfaces. In humans, the neonatal Fc receptor (FcRN) transfers IgGs from mother to fetus during gestation and also plays a role in the regulation of IgG serum levels. Fc receptors have been discovered for all of the Ig classes. Thus there is an FcaR receptor that binds IgA, an FceR that binds IgE (see Figure 4-16 also), an FcSR that binds IgD, IgM is bound by an Fc^R, and several varieties of Fc^R receptors capable of binding IgG and its subclasses are found in humans. In many cases, the crosslinking of these receptors by binding of antigen-antibody complexes results in the initiation of signal-transduction cascades that result in such behaviors as phagocytosis or ADCC. The Fc receptor is often part of a signal-transducing complex that involves the participation of other accessory polypeptide chains. As shown in Figure 4-19, this may involve a pair of 7 chains or, in the case of the IgE receptor, a more complex assemblage of two 7 chains and a p chain. The association of an extracellular receptor with an intracellular signal-transducing unit was seen in the B cell receptor (Figure 4-18) and is a central feature of the T-cell-receptor complex (Chapter 9).
The structure of a number of human Fc-receptors. The Fc-binding polypeptides are shown in blue and, where present, accessory signal-transducing polypeptides are shown in green. The loops in these structures represent portions of the molecule with the characteristic immunoglobulin-fold structure. These molecules appear on the plasma membrane as cell-surface antigens and, as indicated in the figure, many have been assigned CD designations (for clusters of differentiation; see Appendix). [Adapted from M. Daeron, 1999, in The Antibodies, vol. 5, p. 53. Edited by M. Zanetti and J. D. Capra.]
Was this article helpful?