By Levi Clancy for Student Reader on
The various F(c) Receptors are organized by the type of antibody they bind -- F(c)γ Receptors bind IgG (aka γ isotype antibodies) and F(c)ε Receptors bind IgE (aka ε isotype antibodies.
One way antibodies stimulate inflammation and clearing of pathogens is by binding of their F(c) regions to F(c)γ receptors (FcγRs) on effector cells. There are three families of FcγRs: FcγRI, aka CD64; FcγRII, aka CD32; and FcγRIII, aka CD16. FcγRs also stimulate binding and uptake of antigens in human complexes, thus playing an important role in antigen presentation by macrophages and dendritic cells. There is a balance between activator FcγRs and inhibitor FcγRs, with many cells displaying both.
|FcγRI (CD64)||FcγRI is expressed only on macrophages and neutrophils. The FcγRI complex includes a γ or ζ (zeta) chain. Mice with their γ chain genes knocked out do not express FcγRI on macrophages and neutrophils. Once FcγRI is bound, the signal is propagated into the cell via the FcγRI immunoreceptor tyrosene-based activation motif (ITAM), located on the γ (or ζ) chain. In response to binding, the ITAM induces antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis. FcγRI is the only receptor which binds antibodies with high affinity.|
|FcγRIIA (CD32)||Not present in mice, FcγRIIA is expressed on macrophages, neutrophils and eosinophils and has signaling motifs in its cytoplasmic tail. FcγRIIA has an immunoreceptor tyrosene-based activation motif (ITAM) and ligation leads to phagocytosis and, in eosinophils, degranulation.|
|FcγRIIB (CD32)||Although present only on B cells, FcγRIIB is similar to FcγRIIA in that both CD32's have signaling motifs in their cytoplasmic tails. However, FcγRIIB is an inhibitory receptor and contains an immunoreceptor tyrosene-based inhibitor motif (ITIM). Although FcγRs bind the F(c) region antibodies, FcγRIIB only provides an inhibitory response when crosslinked to an entire intact antibody (including the F(ab) fragments). In absence of FcγRIIB -- for example, in FcγRIIB knock-out mice-- there is a significantly higher production of antibodies after antigen exposure. However, FcγRIIB is not the only antibody production regulatory mechanism. A second inhibitory role for FcγRIIB is inhibition of FcεRI-induced mast cell degranulation.|
|FcγRIIIA (CD16)||FcγRIIIA is a transmembrane receptor with a cytoplasmic tail, and is found on monocytes, macrophages, natural killer and T cells. Like FcγRI (aka CD64), the FcγRIIIA complex includes a γ or ζ (zeta) chain. FcγRIIIA is the only FcγR found on natural killer cells.|
|FcγRIIIB (CD16)||FcγRIIIB is bound to neutrophil membranes by a glycosyl phosphatidyl inositol (GPI) anchor. Mice lack FcγRIIIB. FcγRIIB plays an important role in antibody-mediated (humoral) tumor protection. Inhibitory FcγRIIB receptors somehow stimulate production of antibodies specific to tumor antigens.|
High-affinity F(c)&epsilonRI is found on most mast cells and basophils. It is only activated by cross-linked antibodies, meaning only those antibodies which have already bound their complementary antigen. Once this cross-linking occurs, a Ca2+ flux occurs which triggers granules to swell, move to the membrane and burst out (degranulation). This leads to release of leukotrines and prostaglandins.