Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells

Immunity. 2004 Jun;20(6):769-83. doi: 10.1016/j.immuni.2004.05.007.

Abstract

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The mechanism by which IgG reaches luminal secretions and the function of IgG in these locations are unknown. Here, we find that the human neonatal Fc receptor (FcRn) is the vehicle that transports IgG across the intestinal epithelial barrier into the lumen where the IgG can bind cognate antigen. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. These results explain how IgG is secreted onto mucosal surfaces and scavenges luminal antigens for recognition by the immune system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigen-Antibody Complex / immunology
  • Antigen-Antibody Complex / metabolism
  • Antigens / immunology
  • Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Polarity
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dogs
  • Endocytosis
  • Histocompatibility Antigens Class I
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Intestines / immunology
  • Mice
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Protein Transport
  • Rabbits
  • Receptors, Fc / genetics
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism*
  • beta 2-Microglobulin / immunology

Substances

  • Antigen-Antibody Complex
  • Antigens
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc
  • beta 2-Microglobulin
  • Ovalbumin
  • Fc receptor, neonatal