Signal Transduction by Fc ' yRIH ( CD 16 ) Is Mediated through the 3 / Chain

Summal"y To determine the functional role of the two isoforms of Fc3,RIII (CD16) (IliA, 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~RIIIA, a hetero-o[igomeric receptor composed of a ligand-binding subunit c~ and dimeric 3/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, Fc3/RIIIB, which is normally attached to the cell surface via a glycosyl-phosphatidylinositol anchor, was incapable of transducing signals. After crosslinking, Fc3,KIIIA signalling was dependent only upon the 3, chain. Fc3/RIIIA chimeras in which the ol subunit transmembrane and cytoplasmic domains were substituted with the corresponding 3/chain sequences functioned as well as wildtype hetero-oligomeric receptors. These data indicate that the ability of the FcyRIIIA complex to activate the appropriate pathways for cell activation is cell-type restricted and independent of the transmembrane and cytoplasmic domains of the c~ subunit. The presence of the 3/chain is responsible for the assembly of, as well as the signal transduction by, the functional cell surface complex.