A subset of human dendritic cells expresses IgA Fc receptor (CD89), which mediates internalization and activation upon cross-linking by IgA complexes.
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.
Geissmann
F
F
Institut Fédératif de Recherche Necker-Enfants Malades, Unité Mixte de Recherche 8603, Centre National de la Recherche Scientifique/Université Paris-V, France. geissman@necker.fr
Launay
P
P
Pasquier
B
B
Lepelletier
Y
Y
Leborgne
M
M
Lehuen
A
A
Brousse
N
N
Monteiro
R C
RC
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051940:B7-2 Antigen; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D020405:Dermis / Q000276:immunology / Q000378:metabolism; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011961:Receptors, Fc / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D020298:U937 Cells; D015854:Up-Regulation / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; C036832:Fc(alpha) receptor; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D016753:Interleukin-10