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 language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Oct 15 1996|
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