Isolation from Human Placenta of the IgG Transporter, FcRn, and Localization to the Syncytiotrophoblast: Implications for Maternal-Fetal Antibody Transport

James L. Leach, Daniel D. Sedmak, Jeanne M. Osborne, Brian Rahill, Michael Dale Lairmore, Clark L. Anderson

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

The IgG transporter responsible for ferrying maternal IgG across the human placenta to fetal circulation has not been identified, although the human homologue of the neonatal rat Fc receptor (FcRn), a heterodimer with pH-dependent IgG affinity, structurally similar to MHC Class I molecules, was recently proposed as a candidate. Affirming this hypothesis, we describe herein the specific copurification from human placenta of 46- and 14-kDa proteins by IgG affinity at acid pH. The larger protein, characterized by its amino acid sequence and by immunoblot, is the α-chain of human FcRn (hFcRn). The smaller is β2-microglobulin. Their coisolation by ligand affinity suggests that they comprise the hFcRn heterodimer. Placenta sections stained immunohistochemically with anti-hFcRn α-chain peptide Abs show extensive expression of hFcRn in the syncytiotrophoblast and traces in the endothelium and other unidentified cells of the villus stroma. We find α-chain mRNA by Northern analysis in human placenta and in human trophoblast-like cell lines (JEG-3, ED27) but not in a human myelocytic cell line (HL60). We suggest that the placental hFcRn heterodimer may transport IgG to the fetus by a mechanism in which maternal IgG is pinocytosed nonspecifically and then carried to fetal tissues by a pH gradient from acidic endosomes to the pH-neutral basolateral surface of the syncytiotrophoblast. Furthermore, the known characteristics of FcRn suggest a wider function, that it is the receptor postulated by Brambell in the 1960s to regulate tissue and serum IgG concentrations by controlling IgG transport and catabolism.

Original languageEnglish (US)
Pages (from-to)3317-3322
Number of pages6
JournalJournal of Immunology
Volume157
Issue number8
StatePublished - Oct 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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