Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
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.
FcRn, Human IgG1, Immunodeficiency, Lysosomal trafficking, Serum persistence
187-195
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
1 February 2003
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally, Zhou, Jinchun, Ghetie, Victor and Ober, Raimund J.
(2003)
Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans.
International Immunology, 15 (2), .
(doi:10.1093/intimm/dxg018).
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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Published date: 1 February 2003
Keywords:
FcRn, Human IgG1, Immunodeficiency, Lysosomal trafficking, Serum persistence
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Local EPrints ID: 424079
URI: http://eprints.soton.ac.uk/id/eprint/424079
ISSN: 0953-8178
PURE UUID: ab9670e3-0540-4dad-a5e1-bacb624d010a
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Date deposited: 04 Oct 2018 16:30
Last modified: 18 Mar 2024 03:48
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Author:
Jinchun Zhou
Author:
Victor Ghetie
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