ABSTRACT
The neonatal Fc receptor (FcRn) is named for the source from which it was first purified, the intestinal epithelium of neonatal rats. The human homologue of FcRn was first found in the placenta, where is presumably involved in transfer of maternal IgG to the fetus. FcRn has since been found in capillary endothelium, intestinal epithelium and other tissues. More recent data has indicated that FcRn has a function beyond the transfer of maternal IgG--the maintenance of constant serum IgG levels. This review summarizes the status of our knowledge on the structure, expression and function of the neonatal Fc gamma receptor.
Subject(s)
Maternal-Fetal Exchange/immunology , Receptors, IgG/chemistry , Receptors, IgG/physiology , Animals , Animals, Newborn , Female , Humans , Infant, Newborn , Placenta/metabolism , PregnancyABSTRACT
The neonatal Fc receptor, FcRn, is expressed in human placental syncytiotrophoblast, capillary endothelium, intestinal epithelium, and other tissues. By analogy with its role in the mouse, human FcRn is expected to transport maternal IgG to the foetus, and protect circulating IgG from catabolism. The larger subunit of FcRn is homologous to the alpha chains of the major histocompatibility complex (MHC) class I proteins, but is encoded outside the MHC on chromosome 19. We report the isolation of clones encoding the alpha chain of human FcRn from chromosome 19-specific libraries. The sequence revealed a similar organization to classical and non-classical MHC, and MHC-related genes. Compared with classical MHC class I genes, the human FcRn alpha chain gene has expanded by acquiring many repetitive sequences in its introns, including multiple Alu elements in the fourth intron. Primer extension analysis showed that there are two transcription initiation sites in the upstream flanking sequence.
Subject(s)
Infant, Newborn/immunology , Receptors, Fc/genetics , Sequence Analysis, DNA , Transcription, Genetic , Amino Acid Sequence , Animals , Antigens, CD/genetics , Base Sequence , Cloning, Molecular , Exons , Histocompatibility Antigens Class I , Humans , Introns , Mice , Molecular Sequence Data , Physical Chromosome Mapping/methods , Promoter Regions, Genetic , Receptors, Fc/isolation & purificationABSTRACT
The 5'-flanking region of the human FcRn alpha-chain gene was analyzed for its ability to directly express the chloramphenicol acetyltransferase (CAT) reporter gene in NIH3T3 and Lu106 cells. Transient transfection of the CAT constructs revealed that there was promoter activity in the region -660 to +300 of the 5'-flanking sequence. Electrophoretic mobility-shift assays showed that there are functional binding sites for Sp1 or Sp1-like factors, AP1 or a related factor, and additional unidentified proteins in the promoter region.
Subject(s)
Gene Expression Regulation , Promoter Regions, Genetic , Receptors, Fc/genetics , Genes, Reporter , Histocompatibility Antigens Class I , Humans , Transcription Factors/physiologyABSTRACT
The acquisition of maternal antibodies is critical for immunologic defense of the newborn. In humans, maternal IgG is actively transported across the placenta. The receptor responsible for this transport has not been identified definitively. We report the isolation from a placental cDNA library of clones encoding the alpha-chain of an immunoglobulin G (IgG)-Fc receptor (hFcRn) that resembles a class I major histocompatibility complex antigen. The DNA and predicted amino acid sequences are very similar to those of the neonatal rat and mouse intestinal Fc receptors, rFcRn and mFcRn. These receptors mediate transport of maternal IgG from milk to the blood-stream of the suckling rat or mouse. Like rat and mouse FcRn, hFcRn binds IgG preferentially at low pH, which may imply that IgG binds hFcRn in an acidic intracellular compartment during transport across the placenta.
