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International Immunology Advance Access originally published online on February 15, 2006
International Immunology 2006 18(4):525-536; doi:10.1093/intimm/dxh393
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

FcRn mediates elongated serum half-life of human IgG in cattle

Imre Kacskovics1, Zsuzsanna Kis1, Balázs Mayer1, Anthony P. West, Jr2, Noreen E. Tiangco2, Mulualem Tilahun3, László Cervenak4, Pamela J. Bjorkman2, Richard A. Goldsby3, Ottó Szenci5 and Lennart Hammarström6

1 Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary
2 Division of Biology 114-96 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA, USA
3 Department of Biology, Amherst College, Amherst, MA, USA
4 Research Group of Metabolism and Atherosclerosis, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
5 Clinics for Large Animals, Faculty of Veterinary Science, Szent István University, Üllo, Hungary
6 Division of Clinical Immunology, Karolinska Hospital, Huddinge, Sweden

Correspondence to: I. Kacskovics; E-mail: kacskovics.imre{at}aotk.szie.hu

IgG has the longest survival time in the circulation of the Ig classes and the lowest fractional catabolic rate. The neonatal Fc receptor (FcRn) plays an important role in regulating these processes. Recently, we have cloned the bovine neonatal Fc receptor (bFcRn) alpha chain and detected its expression in various epithelial cells which are mediating IgG secretion. However, its function in IgG homeostasis has not been investigated. In the current study, we analyzed the binding affinity of bovine and human IgGs to bFcRn using surface plasmon resonance and by in vitro radioreceptor binding assays. As human IgG binds stronger to the bFcRn, than bovine IgG at pH 6, we subsequently analyzed its catabolism in normal and transchromosomic calves that produce human Igs. Pharmacokinetic studies showed that human IgG had ~33 days serum half-life both in normal and transchromosomic calves, which is more than two times longer than its bovine counterpart. We also demonstrate FcRn expression in endothelial cells and in the kidney which are supposed to be involved in IgG metabolism. These data suggest that bFcRn is involved in IgG homeostasis in cattle and furthermore, that the transchromosomic calves producing human Igs can effectively protect their human IgGs which have implications for successful large-scale production of therapeutic antibodies.

Keywords: antibody, clearance, interaction, therapeutic antibodies, transchromosomic cattle

Transmitting editor: A. Falus


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