ABNORMALLY SHORT SERUM HALF-LIVES OF IGG IN BETA-2-MICROGLOBULIN-DEFICIENT MICE

The MHC class I-related receptor, FcRn, mediates the transfer of mater nal gamma globulin (IgG) to young rodents, primarily via intestinal tr anscytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild-type and mutated Fc-hinge fragments. The site encompasses residues at the CH2-C H3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokineti cs of the Fc-hinge fragments. This suggests that in addition to its kn own function, FcRn might also play a role in IgG homeostasis. Consiste nt with this hypothesis, in this study, we demonstrate that FcRn alpha -chain mRNA is present not only in neonatal brush border but also in o ther tissues of adult animals (liver, lung, spleen and endothelial cel ls). In addition, analysis of the pharmacokinetics of mouse Ig/Fc-hing e fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the beta-phase half-lives are abn ormally short. These findings suggest that FcRn is involved in lgG hom eostasis.