SIGNAL TRANSDUCTION BY FC-GAMMA-RIII (CD16) IS MEDIATED THROUGH THE GAMMA CHAIN

To determine the functional role of the two isoforms of Fc-gamma-RIII (CD16) (IIIA, IIIB), the signal transduction capabilities of wild-type and mutant forms of these receptors were analyzed in transfected lymphoid, myeloid, and fibroblastic cell lines. Functional reconstitution of receptor signalling was observed in hematopoietic T and mast cells, and was absent in nonhematopoietic (CHO) cells. Fc-gamma-RIIIA, a hetero-oligomeric receptor composed of a ligand-binding subunit-alpha and dimeric gamma-chains, generated both proximal and distal responses in jurkat and P815 cells, typical of what is seen in natural killer cells and macrophages upon receptor activation. In contrast, Fc-gamma-RIIIB, which is normally attached to the cell surface via a glycosyl-phosphatidylinositol anchor, was incapable of transducing signals. After crosslinking, Fc-gamma-RIIIA signalling was dependent only upon the gamma-chain. Fc-gamma-RIIIA chimeras in which the alpha-subunit transmembrane and cytoplasmic domains were substituted with the corresponding gamma-chain sequences functioned as well as wild-type hetero-oligomeric receptors. These data indicate that the ability of the Fc-gamma-RIIIA complex to activate the appropriate pathways for cell activation is cell-type restricted and independent of the transmembrane and cytoplasmic domains of the alpha-subunit. The presence of the gamma-chain is responsible for the assembly of, as well as the signal transduction by, the functional cell surface complex.