ISOLATION FROM HUMAN PLACENTA OF THE IGG TRANSPORTER, FCRN, AND LOCALIZATION TO THE SYNCYTIOTROPHOBLAST - IMPLICATIONS FOR MATERNAL-FETAL ANTIBODY TRANSPORT

The IgG transporter responsible for ferrying maternal Ige across the h uman placenta to fetal circulation has not been identified, although t he human homologue of the neonatal rat Fc receptor (FcRn), a heterodim er with pH-dependent IgG affinity, structurally similar to MHC Class I molecules, was recently proposed as a candidate, Affirming this hypot hesis, we describe herein the specific copurification from human place nta of 46- and 14-kDa proteins by IgG affinity at acid pH, The larger protein, characterized by its amino acid sequence and by immunoblot, i s the alpha-chain of human FcRn (hFcRn), The smaller is beta(2)-microg lobulin, Their coisolation by ligand affinity suggests that they compr ise the hFcRn heterodimer, Placenta sections stained immunohistochemic ally with anti-hFcRn alpha-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 alpha-chain mR NA by Northern analysis in human placenta and in human trophoblast-lik e cell lines (JEG-3, ED27) but not in a human myelocytic cell line (HL 60). We suggest that the placental hFcRn heterodimer may transport Ige to the fetus by a mechanism in which maternal IgG is pino-cytosed non specifically and then carried to fetal tissues by a pH gradient from a cidic endosomes to the pH-neutral basolateral surface of the syncytiot rophoblast, Furthermore, the known characteristics of FcRn suggest a w ider function, that it is the receptor postulated by Brambell in the 1 960s to regulate tissue and serum Ige concentrations by controlling Ig G transport and catabolism.