Negative regulation of expression and function of Fc gamma RIII by CD3 zeta in murine NK cells

Fc gamma RIII is involved in Ab-dependent cell-mediated cytotoxicity (ADCC) and cytokine production by NK cells. Signaling and expression of Fc gamma RIII are dependent on FcR gamma, Although NK cells express not only FcR gam ma but also CD3 zeta, the role of CD3 zeta in NK cell function remains uncl ear. Here, we found that the expression of Fc gamma RIII on NK cells from C D3 zeta -deficient mice is unexpectedly up-regulated compared with that on cells from normal mice. Furthermore, ADCC and IFN-gamma production upon Fc gamma RIII-cross-linking by NK cells from CD3 zeta -deficient mice were als o up-regulated. Up-regulation of the surface expression of Fc zeta RIII on CD3 zeta -deficient NK cells is not mediated by transcriptional augmentatio n of either Fc zeta RIII or FcR zeta gene because there was no significant difference in the expression of mRNA for Fc gamma RIII and FcR gamma. Trans fection of CD3 zeta into a cell line expressing Fc gamma RIII and FcR gamma induced a decrease in the cell surface expression of Fc gamma RIII. These findings reveal a negative regulatory role of CD3 zeta in Fc gamma RIII-med iated function of murine NK cells.