A novel subset of NK cells expressing high levels of inhibitory FcγRIIB modulating antibody-dependent function

NK cells can kill antibody-coated target cells following engagement of Fc gamma RIIIA, the major activating Fc gamma R expressed by these cells. The presence of Fc gamma RIIC (CD32C) has also been reported, but its contribution to the Fc gamma R-dependent effector functions of NK cells remains debated. We demonstrate here that inhibitory Fc gamma RIIB is also expressed by a small subset of CD56(+)/NKp46(+) NK cells and can efficiently down-modulate their Fc gamma R-dependent effector function. Immunofluorescence analyses of NK cells from 52 healthy donors showed the presence of CD56(bright)/Fc gamma RII- (5.2% +/- 3.4), CD56(dim)/Fc gamma RIIlo/- (94.1% +/- 3.4), and CD56(dim)/Fc gamma RIIbright (0.64% +/- 0.72) cells. QRT-PCR and protein analyses performed on isolated Fc gamma RIIbright NK cells indicated that Fc gamma RIIB is strongly expressed by these cells but not by Fc gamma RIIlo/- cells. In addition, Fc gamma RIIbright cells showed a weaker antibody-dependent degranulation when incubated with IgG-coated target cells compared with Fc gamma RIIlo/- NK cells, although a strong Fc gamma RIIIA expression was detected in both cells. Furthermore, the addition of anti-Fc gamma RII Fab paralleled a higher degranulation of Fc gamma RIIbright NK cells, indicating a direct role for Fc gamma RIIB in this down-modulating effect. Thus, it is proposed that Fc gamma RIIBbright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating Fc gamma R.J. Leukoc. Biol. 84: 1511-1520; 2008.