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Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism¹

Shreeram Akilesh^*, Gregory J. Christianson, Derry C. Roopenian and Andrey S. Shaw^2,*

^* Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and The Jackson Laboratory, Bar Harbor, ME 04609

The neonatal FcR (FcRn) is a receptor that protects IgG from catabolism and is important in maintaining high serum Ab levels. A major site of expression of FcRn is vascular endothelial cells where FcRn functions to extend the serum persistence of IgG by recycling internalized IgG back to the surface. Because FcRn is expressed in other tissues, it is unclear whether endothelial cells are the only site of IgG protection. In this study, we used FcRn-deficient mice and specific antiserum to determine the tissue distribution of FcRn in the adult mouse. In addition to its expression in the vascular endothelium of several organs, we found FcRn to be highly expressed in bone marrow-derived cells and professional APCs in different tissues. Experiments using bone marrow chimeras showed that FcRn expression in these cells acted to significantly extend the half-life of serum IgG indicating that in addition to the vascular endothelium, bone marrow-derived phagocytic cells are a major site of IgG homeostasis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Medical Scientist Training Program Training Grant T32 GM07200, NIDDK 52701, and 56597. The Core Facility (Washington University School of Medicine Hybridoma Center) was supported in part by the Department of Pathology and Immunology (Washington University School of Medicine) and by National Institutes of Health Grant P30 AR048335.

² Address correspondence and reprint requests to Andrey S. Shaw, Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110. E-mail address: shaw{at}pathbox.wustl.edu

³ Abbreviations used in this paper: FcRn, neonatal FcR; BMDM, bone marrow-derived macrophage; BMDC, bone marrow-derived dendritic cell; BAL, bronchoalveolar lavage.

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