title: Fab fragment glycosylated IgG may play a central role in placental immune evasion.
abstract: OBJECTIVE
  How does the placenta protect the fetus from immune rejection by the mother?
  
  
  CONCLUSIONS
  The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities.
  
  
  BACKGROUND
  The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called 'blocking antibody'.
  
  
  METHODS
  Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study.
  
  
  METHODS
  The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels.
  
  
  RESULTS
  Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property.
  
  
  CONCLUSIONS
  Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy.
  
  
  CONCLUSIONS
  This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer.
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China Department of Pathology, Beijing University Health Science Center, Beijing 100083, China Translational Medicine Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, China 2523381625@qq.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China Department of Pathology, Beijing University Health Science Center, Beijing 100083, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Juping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Zhengshan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Christine
authors.initials: C
authors.lastname: Korteweg
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China Department of Pathology, Beijing University Health Science Center, Beijing 100083, China.
authors.forename: Ruishu
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Dong
authors.affiliation: Translational Medicine Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Monghong
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Gynecology and Obstetrician, First Affiliated Hospital, Shantou University Medical College, Shantou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Fertility, Haidian Maternal and Child Health Hospital, Beijing 100080, China.
authors.forename: Changmei
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Shantou University Medical College, Shantou, Guangdong 515041, China Department of Pathology, Beijing University Health Science Center, Beijing 100083, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Su
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Building 10, Room 5D 37, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Building 10, Room 5D 37, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis / Q000378:metabolism*; D007074:Immunoglobulin G / Q000032:analysis / Q000378:metabolism*; D056747:Immunomodulation; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D018448:Models, Immunological; D010920:Placenta / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D010929:Placentation; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D006023:Glycoproteins
chemical_list: D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: asymmetric immunoglobulin G; fetus; immune evasion; leukocyte; placenta