Localization of the site of the IgG molecule that regulates maternofetal transmission in mice.

Site-directed mutagenesis of a recombinant Fc hinge fragment has recently been used to localize the site of the mouse IgG1 (mIgG1) molecule that is involved in the intestinal transfer of recombinant Fc hinge fragments in neonatal mice. This site encompasses Ile-253, His-310, Gln-311, His-433 and Asn-434, localized at the CH2-CH3 domain interface and overlapping with the staphylococcal protein A-binding and catabolic sites. In the present study, the effect of these mutations on the maternofetal transfer of Fc hinge fragments has been studied. Experiments to analyze transfer of radiolabeled Fc hinge fragments from the circulation of 15-18 day pregnant mice to fetuses in utero demonstrate that the mutations affect the maternofetal transmission in a way that correlates closely with the effects of the mutations on intestinal transfer and catabolism. The studies indicate that the neonatal Fc receptor, FcRn, is involved in transcytosis across both yolk sac and neonatal intestine in addition to the regulation of IgG catabolism.