Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
Abstract
IgG is the most abundant serum antibody and is an essential component of the humoral immune response. It is known that the 'neonatal' Fc receptor (FcRn) plays a role in maintaining constant serum IgG levels by acting as a protective receptor which binds and salvages IgG from degradation. However, the cellular mechanism that is involved in serum IgG homeostasis is poorly understood. In the current study we address this issue by analyzing the intracellular fate in human endothelial cells of IgG molecules which bind with different affinities to FcRn. The studies show that IgG which do not bind to FcRn accumulate in the lysosomal pathway, providing a cellular explanation for short serum persistence of such antibodies. We have also investigated the saturability of the homeostatic system and find that it has limited capacity. Our observations have direct relevance to the understanding and treatment of IgG deficiency, and to the effective application of therapeutic antibodies.
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Endothelial cells are regarded as the major site for IgG salvage in vivo.
“The current study has focused on the behavior of FcRn inhibitors in endothelial cells, since those cells are regarded as the major site for IgG salvage in vivo [3,4].”
From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [4]
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FcRn: the neonatal Fc receptor comes of age
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Population Pharmacokinetics of Therapeutic Monoclonal Antibodies
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An Engineered Human IgG1 Antibody with Longer Serum Half-Life
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Glycosylation and Fc Receptors
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Expression of Neonatal Fc Receptor in the Eye
Powner, M. B., McKenzie, J. A. G., Christianson, G. J., Roopenian, D. C., & Fruttiger, M. (2014) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.13-12574 · Cited by 62 · see citing works
Sirina, J., D'Hooghe, L. E., Singhvi-Hanns, L. A., Cole, S. L., Shock, A., Holliday, N. D., & Stoddart, L. A. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105128
- Authors
- Ward, E. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Ward, E. S.
- ORCID
- Ward, E. S.
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 15
- Issue
- 2
- Pages
- 187-195
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2171136826
- Cited by
- 216
- References
- 1
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 13 · 2023: 14 · 2022: 6 · 2021: 9 · 2020: 14 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 12 · 2012: 10
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI039167, R01AI050747, R01 AI39167, R01 AI/RR 50747)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- neonatal Fc receptor, IgG degradation, lysosomal pathway, endothelial cells, IgG deficiency, therapeutic antibodies, humoral immunity
- MeSH terms
- Antibody Affinity, Homeostasis, Humans, Immunoglobulin G, Receptors, Fc, Histocompatibility Antigens Class I, Serum
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