A subset of human dendritic cells expresses IgA Fc receptor (CD89), which mediates internalization and activation upon cross-linking by IgA complexes

J Immunol. 2001 Jan 1;166(1):346-52. doi: 10.4049/jimmunol.166.1.346.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / metabolism*
  • Antigens, CD / biosynthesis*
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, CD / physiology
  • B7-2 Antigen
  • Binding Sites, Antibody
  • Cells, Cultured
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dermis / immunology
  • Dermis / metabolism
  • Epidermis / immunology
  • Epidermis / metabolism
  • Extracellular Space / immunology
  • Extracellular Space / metabolism
  • Histocompatibility Antigens Class II / biosynthesis
  • Humans
  • Immunoglobulin A / metabolism*
  • Interleukin-10 / metabolism
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism
  • Lymphocyte Activation / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Monocytes / immunology
  • Monocytes / metabolism
  • Protein Binding / immunology
  • Receptors, Fc / biosynthesis*
  • Receptors, Fc / immunology*
  • Receptors, Fc / metabolism
  • Receptors, Fc / physiology
  • U937 Cells
  • Up-Regulation / immunology

Substances

  • Antigen-Antibody Complex
  • Antigens, CD
  • B7-2 Antigen
  • CD86 protein, human
  • Fc(alpha) receptor
  • Histocompatibility Antigens Class II
  • Immunoglobulin A
  • Membrane Glycoproteins
  • Receptors, Fc
  • Interleukin-10