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Cytokine‐regulated expression and inhibitory function of FcγRIIB1 and ‐B2 receptors in human dendritic cells
Author(s) -
Guriec Nathalie,
Daniel Catherine,
Le Ster Karine,
Hardy Elisabeth,
Berthou Christian
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0305155
Subject(s) - biology , immune system , cytokine , receptor , dendritic cell , immunology , tumor necrosis factor alpha , monocyte , microbiology and biotechnology , myeloid , interleukin 10 , biochemistry
Dendritic cells (DC) capture immune complexes (IC) via Fc receptors for immunoglobulin G FcγRII and elicit antigen presentation and protective antitumoral immune response in mice. Two protocols are commonly used to differentiate human monocyte‐derived DC in vitro. They associate granulocyte macrophage‐colony stimulating factor (CM‐CSF) with interleukin (IL)‐4 or IL‐13. In this study, we first assessed the ability of the two types of DCto initiate an immune response against an IC‐linked antigen. We evidenced that IL‐4 and IL‐13 DC display comparable lymphocyte stimulatory capacity and similar lifetimes. We next characterized FcγRIIs expressed by pure populations of circulating myeloid DC (BDCA1+DC), IL‐4, and IL‐13 DC. We highlighted the expression of FcγRIIA, ‐B1, and ‐B2 by pure populations of BDCA1 myeloid DCs and IL‐4 and IL‐13 DC. Moreover, IL‐4 and IL‐13 DC displayed greater FcγRIIB expression than monocytes but a comparable FcγRIIA. We next investigated the FcγRIIB mechanism of action. We evidenced that deleting FcγRIIB increased the ability of IC‐pulsed DC to stimulate autologous lymphocytes. FcγRIIB acted by lowering IC uptake, surface expression of costimulation molecules, and cytokine release. Finally, the balance between activating FcγRIIA/inhibitory FcγRIIB (B1+B2) could be modulated in vitro by inflammation mediators. By lowering FcγRIIB expression without significantly affecting FcγRIIA, prostaglandin E2 (PGE‐2) appeared to be a major regulator of this balance. IL‐1β and tumor necrosis factor α were also found to potentiate PGE‐2 action. Altogether, our results evidence an inhibitory role for FcγRIIB in human DC and provide an easy way to possibly improve in vitro the induction of immune response against IC‐linked antigen.