A novel subset of NK cells expressing high levels of inhibitory Fc{gamma}RIIB modulating antibody-dependent function.

摘要

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