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Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice
Author(s) -
Ghetie Victor,
Hubbard James G.,
Kim JinKyoo,
Tsen MayFang,
Lee Yukfung,
Ward E. Sally
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830260327
Subject(s) - neonatal fc receptor , biology , transcytosis , antibody , receptor , mhc class i , immunoglobulin g , beta 2 microglobulin , immunology , spleen , fragment crystallizable region , microbiology and biotechnology , major histocompatibility complex , immune system , endocytosis , genetics
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.