title: Two ultrastructural distribution patterns of immunoglobulin G in human placenta and functional implications.
abstract: The placenta is known to protect the fetus from infection and maternal rejection. In a previous study, we demonstrated that placental trophoblasts can synthesize immunoglobulin G (IgG). In this study, we investigated the distribution of immunoglobulins (IgG, IgM, and IgA), IgG receptors (FcRn and FcgammaRIII), and complement proteins in placental trophoblasts at the ultrastructural level. In addition, we studied the mRNA expression of IgG1 heavy chain (IGHG1), recombination activating gene 1 (RAG1), RAG2, and activation-induced cytidine deaminase (AID) with nested RT-PCR in primary cultured trophoblasts. The mRNA transcripts of IGHG1, RAG1, RAG2, and AID were all identified in primary trophoblasts, further establishing the IgG-producing capacity of trophoblasts. At the ultrastructural level with colloidal gold-labeled antibodies, IgG was found to be distributed in two distinct locations in syncytiotrophoblasts. For one, it was colocalized with FcRn in endosome displaying low electron density, and for the other it was colocalized with complement C1q in medium-electron density irregular structures that have not been reported previously. This characteristic distribution suggests that IgG is likely processed through two molecular mechanisms in syncytiotrophoblasts: receptor-bound transportation across the syncytiotrophoblast and formation of immune complexes with locally produced IgG. The latter mechanism is probably aimed at neutralizing detrimental maternal anti-paternal major histocompatibility complex antibodies. Our findings support the hypothesis that placenta-produced IgG can selectively react with maternal anti-fetus antibodies and provide a mechanism of fetomaternal tolerance to protect the fetus from maternal immune rejection.
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China Henan Engineering Lab of Antibody Medicine, Henan University Medical College, Kaifeng, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China Department of Pulmonology, Medical Center Haaglanded, the Hague, the Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Korteweg
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China.
authors.forename: Zhengshan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
authors.affiliation: Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, China.
authors.forename: Weiqiu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Center of Translational Medicine (Second Affiliated Hospital), Shantou University Medical College, Shantou, China Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, China Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China jguemailbox@gmail.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
mesh_terms: D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D010920:Placenta / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D014018:Tissue Distribution; D014327:Trophoblasts / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D007074:Immunoglobulin G
keywords: immune complex; immunoglobulin G; placenta; ultrastructure