REQUIREMENT FOR A BETA(2)-MICROGLOBULIN-ASSOCIATED FC RECEPTOR FOR ACQUISITION OF MATERNAL IGG BY FETAL AND NEONATAL MICE

There is considerable evidence to suggest that an FcR similar in struc ture to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG a cross the intestinal epithelium of suckling mice. However, this has no t previously been shown definitively, nor has it been shown whether Fc Rn is the only, or even the major, IgG transporter in the neonatal mou se gut. We report here that neonatal mice homozygous for a targeted di sruption of the beta(2)microglobulin (beta(2)m) gene, which encodes on e subunit of FcRn, had reduced FcRn alpha-chain at the lumenal plasma membrane of intestinal cells. These mice had strikingly lower serum Ig e levels during the First month after birth than littermates that poss essed functional FcRn. Furthermore, we found by fostering mice on moth ers with a different IgG allotype that all of the IgG in sera of beta( 2)m(-/-) mice was endogenous, and that none was obtained from milk. We conclude that FcRn is the only transporter of IgG from mother to youn g in the mouse. The onset of IgG synthesis in mice that received no mi lk IgG lagged behind that in siblings with normal Ige transport, sugge sting that maternal IgG stimulates Ab production in the neonate. We no ted no difference between the IgG concentrations in the milk of beta(2 )m(-/-) and beta(2)m(+/-) mice, indicating that FcRn is not involved i n the secretion of IgG into milk.