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 FcRIIIA, the major activating FcR expressed by these cells. The pres- ence of FcRIIC (CD32C) has also been reported, but its contribution to the FcR-dependent effec- tor functions of NK cells remains debated. We demonstrate here that inhibitory FcRIIB is also expressed by a small subset of CD56/NKp46 NK cells and can efficiently down-modulate their FcR-dependent effector function. Immunofluo- rescence analyses of NK cells from 52 healthy donors showed the presence of CD56 bright /FcRII - (5.2%3.4), CD56 dim /FcRII lo/- (94.1%3.4), and CD56 dim /FcRII bright (0.64%0.72) cells. QRT-PCR and protein analyses performed on iso- lated FcRII bright NK cells indicated that FcRIIB is strongly expressed by these cells but not by FcRII lo/- cells. In addition, FcRII bright cells showed a weaker antibody-dependent degranula- tion when incubated with IgG-coated target cells compared with FcRII lo/- NK cells, although a strong FcRIIIA expression was detected in both cells. Furthermore, the addition of anti-FcRII Fab paralleled a higher degranulation of FcRII bright NK cells, indicating a direct role for FcRIIB in this down-modulating effect. Thus, it is proposed that FcRIIB bright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating FcR. J. Leukoc. Biol. 84: 1511-1520; 2008.