Combined loss of Bim and Bmf causes premature lethality. Cohorts of mice of the indicated genotypes were followed over 18 months. Mice developing overt signs of illness (cachexia, short breath, fuzzy fur, and enlarged lymph nodes or spleen) were killed, and organs were subjected to histopathological assessment in a blinded fashion revealing evidence for autoimmunity and tumor formation in a significant portion of double mutant mice. (A) Kaplan-Meier analysis of disease-free survival. Significant differences of interest (log-rank Mantle-Cox): WT vs Bim^−/− mice (P = .036); WT vs Bim^+/−Bmf^−/− (P = .0074); WT vs Bim^−/−Bmf^+/− (P = .0001); WT vs DKO (P < .0001); WT vs Vav-Bcl2 (P < .0001); Bmf^−/− vs DKO (P = .0009); Bim^−/− vs Bim^−/−Bmf^+/− (P = .0065); Bim^−/− vs DKO (P = .0055); and DKO vs Vav-Bcl2 (P = .032). The relative frequency of autoimmune pathologies and different types of malignancies observed are shown in B and C, respectively. (D) Kaplan-Meier analysis of disease-free survival of C57BL/6 Ly5.1⁺ coisogenic recipients reconstituted with 2 × 10⁶ bone marrow cells of mice of the indicated genotypes (all C57BL/6 Ly5.2⁺) after a single dose of γ-irradiation (9.5 Gy). Significant differences (log-rank Mantle-Cox) were observed between WT vs Bim^−/− (P = .022); WT vs DKO (P < .0001); Bmf^−/− vs Bim^−/− (P = .0262); Bmf^−/− vs DKO (P = .0003); and Bim^−/− vs DKO (P = .0423).