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Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice

Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice
Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice

The MHC class I-related receptor, FcRn, mediates the transfer of maternal gamma globulin (IgG) to young rodents, primarily via intestinal transcytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild-type and mutated Fc-hinge fragments. The site encompasses residues at the CH2-CH3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokinetics of the Fc-hinge fragments. This suggests that in addition to its known function, FcRn might also play a role in IgG homeostasis. Consistent with this hypothesis, in this study, we demonstrate that FcRn α-chain mRNA is present not only in neonatal brush border but also in other tissues of adult animals (liver, lung, spleen and endothelial cells). In addition, analysis of the pharmacokinetics of mouse Ig/Fc-hinge fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the β-phase half-lives are abnormally short. These findings suggest that FcRn is involved in IgG homeostasis.

β2-microglobulin-deficient mice, FcRn, IgG catabolism, Recombinant Fc-hinge fragment
0014-2980
690-696
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Hubbard, James G.
8394863f-e859-4e83-8d13-7f19e5760264
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Tsen, May Fang
ee928224-ae90-4cf6-8a0a-263e7f8ec057
Lee, Yukfung
022fad03-f02b-4e42-8890-f405f1c4eea7
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Hubbard, James G.
8394863f-e859-4e83-8d13-7f19e5760264
Kim, Jin Kyoo
3f679975-b86c-4b96-9571-499c2ad80378
Tsen, May Fang
ee928224-ae90-4cf6-8a0a-263e7f8ec057
Lee, Yukfung
022fad03-f02b-4e42-8890-f405f1c4eea7
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Ghetie, Victor, Hubbard, James G., Kim, Jin Kyoo, Tsen, May Fang, Lee, Yukfung and Ward, E. Sally (1996) Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice. European Journal of Immunology, 26 (3), 690-696. (doi:10.1002/eji.1830260327).

Record type: Article

Abstract

The MHC class I-related receptor, FcRn, mediates the transfer of maternal gamma globulin (IgG) to young rodents, primarily via intestinal transcytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild-type and mutated Fc-hinge fragments. The site encompasses residues at the CH2-CH3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokinetics of the Fc-hinge fragments. This suggests that in addition to its known function, FcRn might also play a role in IgG homeostasis. Consistent with this hypothesis, in this study, we demonstrate that FcRn α-chain mRNA is present not only in neonatal brush border but also in other tissues of adult animals (liver, lung, spleen and endothelial cells). In addition, analysis of the pharmacokinetics of mouse Ig/Fc-hinge fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the β-phase half-lives are abnormally short. These findings suggest that FcRn is involved in IgG homeostasis.

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More information

Published date: April 1996
Keywords: β2-microglobulin-deficient mice, FcRn, IgG catabolism, Recombinant Fc-hinge fragment

Identifiers

Local EPrints ID: 425114
URI: https://eprints.soton.ac.uk/id/eprint/425114
ISSN: 0014-2980
PURE UUID: af5b82cd-b75e-4248-9317-5bac8dc6f9ba
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 11 Oct 2018 16:30
Last modified: 14 Mar 2019 01:21

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Contributors

Author: Victor Ghetie
Author: James G. Hubbard
Author: Jin Kyoo Kim
Author: May Fang Tsen
Author: Yukfung Lee
Author: E. Sally Ward ORCID iD

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