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 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.
Leach
J L
JL
The Ohio State Biochemistry Program, The Ohio State University, Columbus 43210, USA.
Sedmak
D D
DD
Osborne
J M
JM
Rahill
B
B
Lairmore
M D
MD
Anderson
C L
CL
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
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