MATERNALLY DERIVED IMMUNOGLOBULIN LIGHT-CHAIN IS PRESENT IN THE FETALMAMMALIAN CNS

Toward identifying molecules involved in cell-cell interactions during cerebral cortical development, we have investigated the nature of imm unoglobulin-like immunoreactivity (Ig-ir) in the murine cortex. Immuno histochemistry using several antisera recognizing IgG revealed intense immunoreactivity in the subplate and marginal zone of embryonic day 1 6 cortex, as well as in the hindbrain and spinal cord, particularly wi thin ventral fiber tracts. In three independently derived mouse strain s lacking the recombination activating genes RAG-1 or RAG-2, which are essential for Ig production, Ig-ir was absent from the fetal CNS. Wes tern blot analyses of wild-type brains from embryonic day 12 through b irth identified a 25 kDa protein that co-migrated with lg light chain and was absent from RAG-1 or RAG-2 -/- brain samples. This result coul d be replicated with an antiserum specific for lg kappa light chain, b ut not with antisera specific for Ig gamma or mu heavy chain. No Ig-ir was detected in the brains of RAG-1 +/- embryos carried by a -/- fema le, suggesting a maternal source of the immunoreactive molecule. In co nfirmation of this, Ig-ir could be partially reproduced by intraperito neal injection of pregnant RAG-1 -/- females with normal mouse serum. We conclude that maternally derived Ig light chain is present in the f etal murine CNS. This may represent a novel maternal contribution to f etal neural development and implicates Ig molecules as potential media tors of cortical developmental events.