---

Regular Manuscript

2-microglobulin deficient mice catabolize IgG more rapidly than FcRn--chain deficient mice

¹ The Ohio State University

^* To whom correspondence should be addressed. E-mail: anderson.48{at}osu.edu.

	Abstract

FcRn, a nonclassical MHC-I protein bound to 2-microglobulin (2m), diverts IgG and albumin from an intracellular degradative fate, prolonging the half-lives of both. While knockout mouse strains lacking either FcRn--chain (AK) or 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 2m does not affect the IgG production rate, we tested whether an additional 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--chain and 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 2m-expressing AK strain than in the 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 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.

Key Words: steady-state, albumin, half-life, knockout, Fc receptor