Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin.
The major histocompatibility complex class I-related neonatal Fc receptor, FcRn, assembles as a heterodimer consisting of a heavy chain and beta(2)-microglobulin (beta(2)m), which is essential for FcRn function. We observed that, in Madin-Darby canine kidney (MDCK) cells, the function of human FcRn in mediating the bidirectional transport of IgG was significantly increased upon co-expression of the human isoform of beta(2)m. In MDCK cells, the presence of human beta(2)m endowed upon human FcRn an enhanced ability to exit the endoplasmic reticulum and acquire mature carbohydrate side-chain modifications at steady state, a faster kinetics of maturation, and augmented localization at the cell surface as a mature glycoprotein able to bind IgG. Although human FcRn with immature carbohydrate side-chain modifications was capable of exhibiting pH-dependent binding of IgG, only human FcRn with mature carbohydrate side-chain modifications was detected on the cell surface. These results show that human FcRn travels to the cell surface via the normal secretory pathway and that the appropriate expression and function of human FcRn in MDCK cells depends upon the co-expression of human beta(2)m.
Claypool
Steven M
SM
Harvard Medical School, Program in Immunology, Gastroenterogy Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Dickinson
Bonny L
BL
Yoshida
Masaru
M
Lencer
Wayne I
WI
Blumberg
Richard S
RS
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007112:Immunity, Maternally-Acquired / Q000235:genetics; D007074:Immunoglobulin G / Q000378:metabolism*; D007231:Infant, Newborn; D007668:Kidney; D021381:Protein Transport; D011961:Receptors, Fc / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; C100688:Fc receptor, neonatal