FcRn mediates elongated serum half-life of human IgG in cattle.
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 approximately 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.
Kacskovics
Imre
I
Department of Physiology and Biochemistry, Faculty of Veterinary Science, Szent István University, Budapest, Hungary. kacskovics.imre@aotk.szie.hu
Kis
Zsuzsanna
Z
Mayer
Balázs
B
West
Anthony P
AP
Tiangco
Noreen E
NE
Tilahun
Mulualem
M
Cervenak
László
L
Bjorkman
Pamela J
PJ
Goldsby
Richard A
RA
Szenci
Ottó
O
Hammarström
Lennart
L
D000818:Animals; D000915:Antibody Affinity; D001667:Binding, Competitive; D002417:Cattle; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000378:metabolism*; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D011961:Receptors, Fc / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal