Functional significance of the Fas molecule in naive lymphocytes

Abstract

The Fas molecule mediates apoptotic signal In many ceIL types. Mouse mutations (Ipr, Ipi^cg gid), which impair the function of Fas, cause spontaneous autoimmune disease. We generated Fas deficient (Fas^-/-) mice by homologous recombinatlon. In embryonic stem ceILs Fas^-/- mice developed Ipr-like disease, confirming that the abnormality of Faa is causal in the Ipr phenotype. We also made Fas^-/- chlmeric mice composed of a mixture of Fas^+/+ and Fas ceILs^-/-. The chimeric mice also showed the Ipr phenotype. In Fas^-/- chimerlc mice, the Fas-deficient population expanded progressively among mature T and B lymphocytes. The expansion of Fas-deficient lymphocytes occurred at the naive, pre-prlmed, lymphocyte stage. These results suggest that the Fas molecule functions not only after antlgenlc stimulation, as previously hypothesized, but also at the naive lymphocyte stage.