The role of the Brambell receptor (FcRB) in liver: protection of endocytosed immunoglobulin G (IgG) from catabolism in hepatocytes rather than transport of IgG to bile.
The Brambell receptor (FcRB) mediates functions of both immunoglobulin G (IgG) transport, transmitting immunity from mother to young, and IgG protection, making IgG the longest surviving of all plasma proteins. Reflecting its role as transport receptor (termed FcRn, for neonatal rat intestine, the tissue from which it was first cloned), FcRB is expressed antenatally in the rabbit, mouse and rat fetal yolk sac and in human placental syncytiotrophoblasts, and neonatally in the intestinal epithelium of mice and rats. Reflecting its role as protection receptor (FcRp), FcRB is expressed in the vascular endothelium throughout life, where it protects IgG from the on-going catabolic activities of this tissue. FcRB detected in hepatocytes was hypothesized to mediate transport of IgG from serum to bile, thus potentially extending the transport expression (FcRn) of this receptor beyond the perinatal period. Our results show serum-to-bile transport of IgG to be unaffected in mice functionally deleted for FcRB. Accordingly, the hypothesis is rejected that FcRB functions as transport receptor (FcRn) in liver. The default conclusion is that FcRB in hepatocytes functions as FcRp, serving to protect IgG from catabolism in hepatocytes that accompanies the endocytic activity of these cells. We conclude that there remains to date no evidence of an FcRn-like transport function of the Brambell receptor beyond the perinatal period, after which the FcRp function of the receptor predominates, paralleling the endocytic activities of the associated tissues.
Telleman
P
P
Biotherapeutics Development Lab, Harvard Institute of Human Genetics, Harvard Medical School, and Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Junghans
R P
RP
D000818:Animals; D001646:Bile / Q000276:immunology*; D001692:Biological Transport / Q000276:immunology; D004705:Endocytosis / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011961:Receptors, Fc / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011961:Receptors, Fc