Published online before print August 21, 2008

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0608343

Received for publication June 6, 2008.
Revised July 22, 2008.
Accepted for publication July 24, 2008.

Article

A novel subset of NK cells expressing high levels of inhibitory FcRIIB modulating antibody-dependent function

Charles-Antoine Dutertre ^*, Emmanuelle Bonnin-Gélizé ^*, Karen Pulford ^||, Dominique Bourel , Wolf-Herman Fridman ^*, and Jean-Luc Teillaud ^*@

*Intitut National de la Santé de la Recherche Médicale, UMR872, Paris, France; Centre de Recherche des Cordeliers, Université Pierre et Marie Curi-Paris6, UMR S 872, Paris, France; Université Paris Descartes, UMR S 872, Paris, France; Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, France; and ||Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom

^@ To whom correspondence should be addressed. E-mail: jean-luc.teillaud{at}crc.jussieu.fr.

Abstract

NK cells can kill antibody-coated target cells following engagement of FcRIIIA, the major activating FcR expressed by these cells. The presence of FcRIIC (CD32C) has also been reported, but its contribution to the FcR-dependent effector 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. Immunofluorescence 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 isolated 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 degranulation 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.

Key Words: degranulation • Fcgamma receptor • FcgammaRIIB • natural killer cells • natural killer receptors