A novel subset of NK cells expressing high levels of inhibitory Fc?RIIB modulating antibody-dependent function

Abstract

NK cells can kill antibody-coated target cells following engagement of Fc?RIIIA, the major activating Fc?R expressed by these cells. The presence of Fc?RIIC (CD32C) has also been reported, but its contribution to the Fc?R-dependent effector functions of NK cells remains debated. We demonstrate here that inhibitory Fc?RIIB is also expressed by a small subset of CD56+/NKp46+ NK cells and can efficiently down-modulate their Fc?R-dependent effector function. Immunofluorescence analyses of NK cells from 52 healthy donors showed the presence of CD56 bright/Fc?RII-(5.2%±3.4), CD56dim/ Fc?RIIlo/- (94.1%±3.4), and CD56dim/ Fc?RIIbright (0.64%±0.72) cells. QRT-PCR and protein analyses performed on isolated Fc?RIIbright NK cells indicated that Fc?RIIB is strongly expressed by these cells but not by Fc?RIIlo/- cells. In addition, Fc?RIIbright cells showed a weaker antibody-dependent degranulation when incubated with IgG-coated target cells compared with Fc?RIIlo/- NK cells, although a strong Fc?RIIIA expression was detected in both cells. Furthermore, the addition of anti-Fc?RII Fab paralleled a higher degranulation of Fc?RIIbright NK cells, indicating a direct role for Fc?RIIB in this down-modulating effect. Thus, it is proposed that Fc?RIIBbright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating Fc?R. © Society for Leukocyte Biology.