DISTINCT PATTERNS OF FAS CELL-SURFACE EXPRESSION DURING DEVELOPMENT OF T-LYMPHOCYTE OR B-LYMPHOCYTE LINEAGES IN NORMAL, SCID, AND MUTANT MICE LACKING OR OVEREXPRESSING P53, BCL-2, OR RAG-2 GENES

Fas is a cell membrane protein involved in programmed cell death. In n ormal young mice, Fas was expressed on pluripotent stem cells, multipo tent progenitors, pro-T and pre-T cells, most thymocytes, and a subset of CD4 and CD8 mature T lymphocytes. In contrast, Fas expression was switched off in B-cell and myelocytic progenitors and most pro-B and a proportion of pre-B cells and was switched on again later, but this o ccurred only in a subset of mature B lymphocytes, A lack of bcl-2 incr eased the proportion of Fas(+) B-lymphocyte lineage cells and Fas(+) C D4(+) cells and decreased the percentage of Fas(-) CD8(+) mature T-cel l subsets, Overexpression of bcl-2 reversed this pattern of Fas cell s urface expression. Interestingly, lack of p53 increased the proportion s of Pas-expressing CD4 and CD8 mature T-cell subsets and of Fas(-) B- cell precursors but decreased that of Fas(-) mature B-lymphocyte popul ations, We conclude that the expression of Fas is regulated distinctly during the development of T and B lymphocytes. Although the products of neither bcl-2 nor p53 genes are essential for pas cell surface expr ession on hematopoietic cells, these repressor and effector genes, res pectively, of programmed cell death affect distinct subsets of lymphoi d lineage cells at different stages of lymphopoiesis, Our results sugg est that distinct combinations of effector and suppressor genes of pro grammed cell death act on distinct cell populations and at different s tages of differentiation within the same cell lineage in the hematopoi etic system.