title: Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport.
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 alpha-chain of human FcRn (hFcRn). The smaller is beta2-microglobulin. Their coisolation by ligand affinity suggests that they comprise the hFcRn heterodimer. Placenta sections stained immunohistochemically 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 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.
authors.affiliation: The Ohio State Biochemistry Program, The Ohio State University, Columbus 43210, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Leach
authors.forename: D D
authors.initials: DD
authors.lastname: Sedmak
authors.forename: J M
authors.initials: JM
authors.lastname: Osborne
authors.forename: B
authors.initials: B
authors.lastname: Rahill
authors.forename: M D
authors.initials: MD
authors.lastname: Lairmore
authors.forename: C L
authors.initials: CL
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D005260:Female; D015395:Histocompatibility Antigens Class I; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007112:Immunity, Maternally-Acquired; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011961:Receptors, Fc / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology; D001613:beta 2-Microglobulin / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D001613:beta 2-Microglobulin; C100688:Fc receptor, neonatal