10-21 The Fc receptors of accessory cells are signaling receptors specific for immunoglobulins of different classes.
The Fc receptors are a family of cell-surface molecules that bind the Fc portion of immunoglobulins. Each member of the Fc family recognizes immunoglobulin of one or a few closely related heavy-chain isotypes through a recognition domain on the α chain of the Fc receptor. Most Fc receptors are themselves members of the immunoglobulin gene superfamily. Different cell types bear different sets of Fc receptors, and the isotype of the antibody thus determines which types of cells will be engaged in a given response. The different Fc receptors, the cells that express them, and their specificities for different antibody classes are shown in Fig. 10.38.
Most Fc receptors function as part of a multisubunit complex. Only the α chain is required for antibody recognition; the other chains are required for transport of the receptor to the cell surface and for signal transduction when an Fc region is bound. Some Fcγ receptors, the Fcα receptor I, and the high-affinity receptor for IgE (FcεRI) all use a γ chain for signaling. This chain, which is closely related to the ζ chain of the T-cell receptor complex (see Section 7-7), associates noncovalently with the Fc-binding α chain. The human FcγRII-A is a single-chain receptor in which the cytoplasmic domain of the α chain replaces the function of the γ chain. FcγRII-B1 and FcγRII-B2 are also single-chain receptors, but function as inhibitory receptors because they contain an ITIM that engages the inositol 5ʹ-phosphatase SHIP (see Section 7-25). The most prominent function of Fc receptors is the activation of accessory cells to attack pathogens, but they also contribute in other ways to immune responses. For example, FcγRII-B receptors negatively regulate the activities of B cells, mast cells, macrophages, and neutrophils by adjusting the threshold at which immune complexes will activate these cells. Fc receptors expressed by dendritic cells enable them to ingest antigen:antibody complexes efficiently and thus process these antigens and present their peptides to T cells.