Transfer of antibodies directed to paternal major histocompatibility class I antigens from pregnant mice to the developing fetus.

Abstract

The placental transmission of antibodies directed toward paternal MHC Class I antigens to the developing fetus was studied to assess their effect on the expression of MHC antigens during fetal development and on the development of immune function. 125I-monoclonal anti-paternal MHC antibodies injected i.v. into pregnant mice on day 15 of gestation were efficiently transferred to the fetus within 24 hr in a dose-dependent manner. Biochemical studies on the transferred radioactivity showed that intact antibodies accumulated in the fetus for up to 3 days after antibody injection. During the same period, antibodies were eliminated from the maternal system. The transfer and accumulation of anti-MHC antibodies were independent of the MHC haplotype of the fetus. The pathway of antibody transfer and the localization of transmitted antibodies in the fetus were studied by autoradiographic analysis of the entire fetoplacental unit 24 hr after the injection of anti-paternal MHC antibodies. Our results indicate that antibodies are transferred by way of the placenta and yolk sac, and reach the fetus predominantly via the circulation. Within the embryo proper, the highest levels of antibody were found in the order of blood greater than thymus greater than fetal liver. Most other fetal organs, with the exception of brain and cartilage, showed antibody accumulation, but to a lesser extent. This pattern of antibody distribution over different tissues was similar for allogeneic and syngeneic fetuses. These findings demonstrate that various fetal tissues, including developing lymphoid cells can be directly exposed to the maternally transmitted anti-MHC antibodies, with possible functional consequences on the development of the fetal immune system.