FUNCTIONAL-SIGNIFICANCE OF THE FAS MOLECULE IN NAIVE LYMPHOCYTES

The Fas molecule mediates apoptotic signal in many cell types, Mouse m utations (lpr, lpr(cg), gld), which impair the function of Fas, cause spontaneous autoimmune disease, We generated Fas-deficient (Fas(-/-)) mice by homologous recombination, In embryonic stem cells Fas(-/-) mic e developed lpr-like disease, confirming that the abnormality of Fas i s causal in the Ipr phenotype, We also made Fas(-/-) chimeric mice com posed of a mixture of Fas(+/+) and Fas(-/-) cells, The chimeric mice a lso showed the lpr phenotype. In Fas(-/-) chimeric mice, the Fas-defic ient population expanded progressively among mature T and B lymphocyte s. The expansion of Fas-deficient lymphocytes occurred at the naive, p re-primed, lymphocyte stage. These results suggest that the Fas molecu le functions not only after antigenic stimulation, as previously hypot hesized, but also at the naive lymphocyte stage.