Proapoptotic Bcl-2 relative bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity

Apoptosis can be triggered by members of the Bcl-2 protein family, such as Bim, that share only the BH3 domain with this family. Gene targeting in mic e revealed important physiological lores for sim. Lymphoid and myeloid cell s accumulated, T cell development was perturbed, and most older mice accumu lated plasma cells and succumbed to autoimmune kidney disease. Lymphocytes were refractory to apoptotic stimuli such as cytokine deprivation, calcium ion flux, and microtubule perturbation but not to others. Thus, Bim is requ ired for hematopoietic homeostasis and as a barrier to autoimmunity. Moreov er, particular death stimuli appear to activate apoptosis through distinct BH3-only proteins.