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The Journal of Immunology, 2001, 166: 346-352.
Copyright © 2001 by The American Association of Immunologists

A Subset of Human Dendritic Cells Expresses IgA Fc Receptor (CD89), Which Mediates Internalization and Activation Upon Cross-Linking by IgA Complexes

Frédéric Geissmann2,3,*,{ddagger}, Pierre Launay2,{dagger}, Benoit Pasquier{dagger}, Yves Lepelletier*, Michelle Leborgne{ddagger}, Agnès Lehuen{dagger}, Nicole Brousse{ddagger} and Renato C. Monteiro{dagger}

Institut Fédératif de Recherche Necker-Enfants Malades, * Unité Mixte de Recherche 8603, Centre National de la Recherche Scientifique/Université Paris-V, {dagger} Institut National de la Santé et de la Recherche Médicale, Unité 25, and {ddagger} Pathology Department, Hôpital Necker-Enfants Malades, Faculté Necker, Université Paris-V, Paris, France

Immature dendritic cells (DC) sample Ags within nonlymphoid tissues and acquire exogenous proteins/pathogens via scavenger receptors or Ig FcR such as Fc{gamma}R and Fc{epsilon}R. IgA is present in a significant proportion among serum Ig and is the main isotype in mucosae, where DC are numerous. We found that a functional Fc{alpha}R (CD89) was expressed in situ and in vitro on interstitial-type DC but not on Langerhans cell-type DC. Interstitial-type DC expressed CD89 as a 50- to 75-kDa glycoprotein with a 32-kDa protein core, which was down-regulated upon addition of TGF-{beta}1. DC, Fc{alpha}R specifically, bound IgA1 and IgA2. Cross-linking of CD89 on DC triggered endocytosis in time-dependent manner. In addition, internalization of polymeric IgA complexes induced the production of IL-10 and DC activation, as reflected by up-regulation of CD86 costimulatory molecules, class II MHC expression, and increased allostimulatory activity. Therefore, interstitial-type DC may use Fc{alpha}R-mediated Ag sampling in the subepithelium to check tissue integrity while Langerhans cells inside epithelial layers may neglect IgA immune complexes.




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