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Charles-Antoine Dutertre, Emmanuelle Bonnin-Gélizé, Karen Pulford, Dominique Bourel, Wolf-Herman Fridman, Jean-Luc Teillaud, A novel subset of NK cells expressing high levels of inhibitory FcγRIIB modulating antibody-dependent function, Journal of Leukocyte Biology, Volume 84, Issue 6, Dec 2008, Pages 1511–1520, https://doi.org/10.1189/jlb.0608343
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Abstract
NK cells can kill antibody-coated target cells following engagement of FcγRIIIA, the major activating FcγR expressed by these cells. The presence of FcγRIIC (CD32C) has also been reported, but its contribution to the FcγR-dependent effector functions of NK cells remains debated. We demonstrate here that inhibitory FcγRIIB is also expressed by a small subset of CD56+/NKp46+ NK cells and can efficiently down-modulate their FcγR-dependent effector function. Immunofluorescence analyses of NK cells from 52 healthy donors showed the presence of CD56bright/FcγRII− (5.2%±3.4), CD56dim/FcγRIIlo/- (94.1%±3.4), and CD56dim/FcγRIIbright (0.64%±0.72) cells. QRT-PCR and protein analyses performed on isolated FcγRIIbright NK cells indicated that FcγRIIB is strongly expressed by these cells but not by FcγRIIlo/- cells. In addition, FcγRIIbright cells showed a weaker antibody-dependent degranulation when incubated with IgG-coated target cells compared with FcγRIIlo/- NK cells, although a strong FcγRIIIA expression was detected in both cells. Furthermore, the addition of anti-FcγRII Fab paralleled a higher degranulation of FcγRIIbright NK cells, indicating a direct role for FcγRIIB in this down-modulating effect. Thus, it is proposed that FcγRIIBbright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating FcγR.
