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An IgG‐transporting Fc receptor expressed in the syncytiotrophoblast of human placenta
Abstract
During normal human pregnancy, maternal IgG crosses the placenta and provides passive immunity for the fetus. In so doing, IgG passes through two cellular barriers: the syncytiotrophoblast and the fetal capillary endothelium. The Fc region of IgG is required for its transport across the placenta, but the Fc receptors responsible have not been identified definitively. We recently reported the isolation from a placental cDNA library of clones encoding the alpha 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 transport of maternal IgG to the fetus and the neonate. We report here the localization of human FcRn mRNA within the placenta by in situ hybridization, and of human FcRn protein by immunohistochemistry. Both methods show that human FcRn is expressed in syncytiotrophoblast, and is, thus, appropriately located to transport maternal IgG across the first barrier. We confirm previous findings that specific binding of IgG to placental 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 the presence of FcRn in syncytiotrophoblast. We propose a transport model in which maternal IgG binds FcRn at low pH in endosomes within the syncytiotrophoblast. FcRn is not expressed in fetal capillary endothelia, and the mechanism of IgG transport across the second barrier remains unknown.
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“Various studies using immunohistochemical staining of placental sections with anti-FcRn antibodies have shown a mix of some (61, 62) or no (36).”
From Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy (2017) · cites this paper as [36]
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Dumont, J. A., Jin, X., Peters, R., Luk, A. Y., Pierce, G. F., & Bitonti, A. J. (2012) · Wiley eBooks · doi:10.1002/9783527644827.ch10 · Cited by 1
The role of Toll-like receptors in the development of immunological tolerance in neonates
Patrascan, C. C. (2010) · Publikationsserver (Universitat Marburg) · doi:10.17192/z2010.0376 · Cited by 1
Challenges in the Pharmacokinetics of Therapeutic Proteins
Limothai, W. (2015) · doi:10.21007/etd.cghs.2015.0184 · Cited by 1
The Diverse Roles of FcRn: Implications for Antibody Engineering
Ward, E. S., & Ober, R. J. (2012) · Wiley eBooks · doi:10.1002/9783527644827.ch11 · Cited by 1
The Biology of the Neonatal Fc Receptor (FcRn)
Kim, J. (2012) · Wiley eBooks · doi:10.1002/9783527644827.ch8
Multifactorial aspects of antibody-mediated blood cell destruction
Kapur, R. (2014) · UvA-DARE (University of Amsterdam)
Influence of the antibody variable domain on FcRn-dependent pharmacokinetics
Schoch, A. (2014) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.17528
Mass spectrometry-based studies for the investigation of protein structure and dynamics
Edgeworth, M. J. (2026) · Warwick Research Archive Portal (University of Warwick) · doi:10.82444/warw.33696577
Metadata
- Authors
- Simister, N. E., Story, C. M., Chen, H., & Hunt, J. S.
- Affiliations
- Brandeis University (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Simister, Neil E.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 1996-07
- Volume
- 26
- Issue
- 7
- Pages
- 1527-1531
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1986652140
- Cited by
- 332
- References
- 43
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 14 · 2023: 7 · 2022: 18 · 2021: 16 · 2020: 14 · 2019: 15 · 2018: 17 · 2017: 13 · 2016: 13 · 2015: 10 · 2014: 13 · 2013: 10 · 2012: 14
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd026429-08)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 26429, R01HD027691, HD27691)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- neonatal Fc receptor, syncytiotrophoblast, placenta, IgG transport, endosomal recycling
- MeSH terms
- Amino Acid Sequence, Binding Sites, Antibody, Biological Transport, Female, Humans, Hydrogen-Ion Concentration, Immunoglobulin Fc Fragments, Membranes, Molecular Sequence Data, Pregnancy, RNA, Messenger, Trophoblasts, Receptors, IgG
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