Published online before print August 21, 2008

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(Journal of Leukocyte Biology. 2008;84:1511-1520.)
© 2008 by Society for Leukocyte Biology

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^*,,,1

^* Intitut National de la Santé et de la Recherche Médicale, UMR S 872, Paris, France;
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, 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

¹ Correspondence: Team 14, Cordeliers Research Centre, UMR S 872, 15 rue de l’Ecole de Médecine, 75270 Paris, cedex 06, France. E-mail: jean-luc.teillaud{at}crc.jussieu.fr

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