Beta 2-microglobulin deficient mice catabolize IgG more rapidly than FcRn- alpha-chain deficient mice.
FcRn, a nonclassical MHC-I protein bound to beta 2-microglobulin (beta 2m), diverts IgG and albumin from an intracellular degradative fate, prolonging the half-lives of both. While knockout mouse strains lacking either FcRn-alpha-chain (AK) or beta 2m (BK) show much shorter half-lives of IgG and albumin than normal mice, the plasma IgG half-life in the BK and AK strains is different, being shorter in the BK strain. Since beta 2m does not affect the IgG production rate, we tested whether an additional beta 2m-associated mechanism protects IgG from catabolism. First, we compared the fractional disappearance rate in plasma of an intravenous dose of radioiodinated IgG in a mouse strain deficient in both FcRn-alpha-chain and beta 2m (ABK), in the two parental knockout strains (AK and BK), and in the background wild-type (WT) strain. We found that IgG survived longer in the beta 2m-expressing AK strain than in the beta 2m-lacking ABK and BK strains, whereas the IgG half-lives between the ABK and BK strains were identical. Then we compared endogenous concentrations of four typical plasma proteins among the four strains and found that steady-state plasma concentrations of both IgG and albumin were higher in the AK strain than in either the BK or the ABK strain. These results suggest that a beta 2m-associated effect other than FcRn prolongs the survival of both IgG and albumin, although leaky gene transcription in the AK strain cannot be ruled out.
Kim
Jonghan
J
Department of Internal Medicine, The Ohio State University, 012K Davis Heart and Lung Research Institute, 473 West Twelfth Avenue, Columbus, OH 43210, USA.
Bronson
C L
CL
Wani
Manzoor A
MA
Oberyszyn
Tatiana M
TM
Mohanty
Sudhasri
S
Chaudhury
Chaity
C
Hayton
William L
WL
Robinson
John M
JM
Anderson
Clark L
CL
D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011961:Receptors, Fc / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011961:Receptors, Fc; D001613:beta 2-Microglobulin; C100688:Fc receptor, neonatal