A novel subset of NK cells expressing high levels of inhibitory FcgammaRIIB modulating antibody-dependent function.
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 CD56bright/FcgammaRII(-) (5.2%+/-3.4), CD56dim/FcgammaRII(lo/-) (94.1%+/-3.4), and CD56dim/FcgammaRIIbright (0.64%+/-0.72) cells. QRT-PCR and protein analyses performed on isolated FcgammaRIIbright NK cells indicated that FcgammaRIIB is strongly expressed by these cells but not by FcgammaRII(lo/-) cells. In addition, FcgammaRIIbright 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 FcgammaRIIbright NK cells, indicating a direct role for FcgammaRIIB in this down-modulating effect. Thus, it is proposed that FcgammaRIIBbright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating FcgammaR.
Dutertre
Charles-Antoine
CA
Intitut National de la Santé et de la Recherche Médicale, UMR S 872, Paris, France.
Bonnin-Gélizé
Emmanuelle
E
Pulford
Karen
K
Bourel
Dominique
D
Fridman
Wolf-Herman
WH
Teillaud
Jean-Luc
JL
D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D018929:Cell Culture Techniques; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D047468:Immunoprecipitation; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D016131:Lymphocyte Subsets; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG