Puma mediates γ-radiation–induced apoptosis of mature T and B lymphocytes and B-cell precursors in vivo. Animals of the indicated genotypes were left untreated or exposed to the indicated doses of whole-body γ-radiation and killed 20 hours thereafter. Spleen and bone marrow were harvested, and the single-cell suspensions were counted and stained with fluorescence-conjugated antibodies specific for CD4 and CD8 to identify mature T cells or IgM and IgD to identify mature B cells using a flow cytometer. Bone marrow suspensions were stained using antibodies recognizing B220, IgM, and CD43 in order to identify pre-B-cell precursors. The total cellularity of CD4⁺ T cells, CD8⁺ T cells, IgM⁺D⁺ B cells in spleen (A-C), and B220⁺sIgM⁺CD43^- pre-B cells found in the bone marrow of both femora (D) is depicted. Bars represent means ± SE of 4 to 10 animals of each genotype and treatment regimen used in at least 4 independent experiments. Statistically significant differences are as follows: (A) CD4⁺ T cells: wt versus Puma^-/- (P < .001), wt versus Bim^-/- (P < .012), wt versus vav-BCL2 (P < .001); (B) CD8⁺ T cells: wt versus Puma^-/- (P < .007), wt versus Bim^-/- (P < .013), wt versus vav-BCL2 (P < .002); (C) IgM⁺D⁺ B cells: wt versus Puma^-/- (P < .001), wt versus Bim^-/- (P < .029), wt versus vav-BCL2 (P < .001); (D) B220⁺sIgM^-CD43^- pre B cells: wt versus Puma^-/- (P < .001), wt versus vav-BCL2 (P < .002).