AN IGG-TRANSPORTING FC RECEPTOR EXPRESSED IN THE SYNCYTIOTROPHOBLAST OF HUMAN PLACENTA

During normal human pregnancy, maternal IgG crosses the placenta and p rovides passive immunity for the fetus. In so doing, IgG passes throug h two cellular barriers: the syncytiotrophoblast and the fetal capilla ry endothelium. The Fc region of IgG is required for its transport acr oss the placenta, but the Fc receptors responsible have not been ident ified definitively. We recently reported the isolation from a placenta l cDNA library of clones encoding the ct chain of a human homologue of the major histocompatibility complex class I-related Fc receptor, the neonatal Fc receptor (FcRn). In mice, FcRn is essential for the trans port of maternal IgG to the fetus and the neonate. We report here the localization of human FcRn mRNA within the placenta by in situ hybridi zation, and of human FcRn protein by immunohistochemistry. Both method s show that human FcRn is expressed in syncytiotrophoblast, and is, th us, appropriately located to transport maternal IgG across the first b arrier. We confirm previous findings that specific binding of IgG to p lacental membranes is greater at pH 6.0 than pH 7.5. This corresponds with the pH dependence of IgG binding to FcRn and is consistent with t he presence of FcRn in syncytiotrophoblast. We propose a transport mod el in which maternal IgG binds FcRn at low pH in endosomes within the syncytiotrophoblast. FcRn is not expressed in fetal capillary endothel ia, and the mechanism of IgG transport across the second barrier remai ns unknown.