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

Authors

  • Victor Ghetie,

    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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  • James G. Hubbard,

    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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  • Jin-Kyoo Kim,

    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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  • May-Fang Tsen,

    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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  • Yukfung Lee,

    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
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  • E. Sally Ward

    Corresponding author
    1. Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
    • Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8576, USA (Fax: +1 214 648 1259)
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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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