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ORIGINAL RESEARCH ARTICLE

β2-Microglobulin Deficient Mice Catabolize IgG More Rapidly Than FcRn--Chain Deficient Mice

Jonghan Kim^*,, C. L. Bronson^*,, Manzoor A. Wani^*, Tatiana M. Oberyszyn, Sudhasri Mohanty^*, Chaity Chaudhury^*, William L. Hayton, John M. Robinson^|| and Clark L. Anderson^*,1

^* Department of Internal Medicine, College of Pharmacy, Department of Evolution, Ecology and Organismal Biology, Department of Pathology, and ^|| Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210

To whom requests for reprints should be addressed at ¹ Department of Internal Medicine, The Ohio State University, 012K Davis Heart and Lung Research Institute, 473 West Twelfth Avenue, Columbus, OH 43210. E-mail: anderson.48{at}osu.edu

FcRn, a nonclassical MHC-I protein bound to β2-microglobulin (β2m), 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 β2m (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 β2m does not affect the IgG production rate, we tested whether an additional β2m-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 β2m (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 β2m-expressing AK strain than in the β2m-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 β2m-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