PT - JOURNAL ARTICLE AU - Bouillet, Philippe AU - Metcalf, Donald AU - Huang, David C. S. AU - Tarlinton, David M. AU - Kay, Tom W. H. AU - Köntgen, Frank AU - Adams, Jerry M. AU - Strasser, Andreas TI - Proapoptotic Bcl-2 Relative Bim Required for Certain Apoptotic Responses, Leukocyte Homeostasis, and to Preclude Autoimmunity AID - 10.1126/science.286.5445.1735 DP - 1999 Nov 26 TA - Science PG - 1735--1738 VI - 286 IP - 5445 4099 - http://science.sciencemag.org/content/286/5445/1735.short 4100 - http://science.sciencemag.org/content/286/5445/1735.full SO - Science1999 Nov 26; 286 AB - 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 mice revealed important physiological roles for Bim. Lymphoid and myeloid cells accumulated, T cell development was perturbed, and most older mice accumulated 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 required for hematopoietic homeostasis and as a barrier to autoimmunity. Moreover, particular death stimuli appear to activate apoptosis through distinct BH3-only proteins.