title: Cytokine-regulated expression and inhibitory function of FcgammaRIIB1 and -B2 receptors in human dendritic cells.
abstract: Dendritic cells (DC) capture immune complexes (IC) via Fc receptors for immunoglobulin G FcgammaRII 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 DC to 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 FcgammaRIIs expressed by pure populations of circulating myeloid DC (BDCA1+DC), IL-4, and IL-13 DC. We highlighted the expression of FcgammaRIIA, -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 FcgammaRIIB expression than monocytes but a comparable FcgammaRIIA. We next investigated the FcgammaRIIB mechanism of action. We evidenced that deleting FcgammaRIIB increased the ability of IC-pulsed DC to stimulate autologous lymphocytes. FcgammaRIIB acted by lowering IC uptake, surface expression of costimulation molecules, and cytokine release. Finally, the balance between activating FcgammaRIIA/inhibitory FcgammaRIIB (B1+B2) could be modulated in vitro by inflammation mediators. By lowering FcgammaRIIB expression without significantly affecting FcgammaRIIA, prostaglandin E2 (PGE-2) appeared to be a major regulator of this balance. IL-1beta and tumor necrosis factor alpha were also found to potentiate PGE-2 action. Altogether, our results evidence an inhibitory role for FcgammaRIIB in human DC and provide an easy way to possibly improve in vitro the induction of immune response against IC-linked antigen.
authors.affiliation: Cellular Therapy Laboratory, Brest Medical School, France. nguriec@voila.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guriec
authors.forename: Catherine
authors.initials: C
authors.lastname: Daniel
authors.forename: Karine
authors.initials: K
authors.lastname: Le Ster
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hardy
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000276:immunology; D020298:U937 Cells
chemical_list: D000936:Antigen-Antibody Complex; D016207:Cytokines; C489017:FCGR1A protein, human; D017452:Receptors, IgG; D015232:Dinoprostone