Recombinant Human Fc gamma RIIIB/CD16b Protein

Receptors for the Fc region of IgG (Fc gamma R) are members of the Ig superfamily. Based on their genetic organization and molecular structure, three classes of human Fc gamma Rs: RI (CD64), RII (CD32), and RIII (CD16), which generate multiple isoforms, are recognized (1 - 3). These receptors function in the activation or inhibition of immune responses. The activating-type receptor either has, or associates non-covalently with an accessory subunit (FcR gamma or zeta chain) that has an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. In contrast, the inhibitory receptor (Fc gamma RIIB) has a built-in immunoreceptor tyrosine-based inhibitory motif (ITIM) in its own cytoplasmic domain. Fc gamma RI is a high-affinity receptor that binds monomeric IgG. Both Fc gamma RII and RIII are low-affinity receptors that bind IgG in the form of immune complexes. Two genes for human Fc gamma RIII, A and B, encoding a transmembrane receptor and a glycosylphosphatidylinositol (GPI) anchored protein, respectively, have been identified. Three allelic variants of Fc gamma RIIIB, NA-1, NA-2, and SH, exist. A soluble form of Fc gamma RIIIB corresponding to the extracellular region of the receptor is produced by proteolytic cleavage and circulates in plasma and other body fluids. The extracellular domains of Fc gamma RIIIA and B share 97% amino acid sequence homology. Whereas Fc gamma RIIIA is expressed on most effector cells of the immune system including macrophage, monocyte, NK cells, mast cells, eosinophils, dendritic cells and Langerhans cells, Fc gamma RIIIB is selectively expressed in neutrophils and eosinophils. Signaling through Fc gamma RIIIA results in oxidative burst, cytokine release and phagocytosis by macrophages, antibody-dependent cellular cytotoxicity by natural killer cells and degranulation of mast cells. By contrast, Fc gamma RIIIB is a decoy receptor that binds IgG complexes without triggering activation. Soluble Fc gamma RIIIB has a regulatory role in inflammatory processes (4). It interacts with complement receptors CR3 and CR4 on monocytes to induce the production of pro-inflammatory cytokines.