Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice.
The MHC class I-related receptor FcRn regulates the levels and persistence of IgG in vivo. This receptor salvages IgG from lysosomal degradation within cells, and the binding properties of an IgG for FcRn correlate with in vivo half-life. FcRn is expressed at multiple different sites throughout adult life. However, the cell types and sites at which FcRn maintains IgG homeostasis are not well defined. Toward understanding the sites of FcRn function, we have generated a mouse strain in which this Fc receptor can be conditionally deleted. In combination with mice that express Cre recombinase under the control of the Tie2 promoter (Tie2-Cre), the effect of site-specific deletion of floxed FcRn in endothelial and hematopoietic cells on IgG persistence was analyzed. The pharmacokinetics and steady-state levels of IgG in Tie2-Cre mice that are homozygous for the floxed FcRn allele reveal a complete loss of FcRn function in regulating the half-lives of wild-type IgG. The primary sites for the maintenance of endogenous IgGs in mice are therefore endothelial and hematopoietic cells.
Montoyo
Héctor Pérez
HP
Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.
Vaccaro
Carlos
C
Hafner
Martin
M
Ober
Raimund J
RJ
Mueller
Werner
W
Ward
E Sally
ES
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D017353:Gene Deletion; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D042810:Receptor, TIE-1 / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020349:Surface Plasmon Resonance
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D042810:Receptor, TIE-1; C100688:Fc receptor, neonatal