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 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.
Bouillet
P
P
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
Metcalf
D
D
Huang
D C
DC
Tarlinton
D M
DM
Kay
T W
TW
Köntgen
F
F
Adams
J M
JM
Strasser
A
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001327:Autoimmune Diseases / Q000209:etiology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005260:Female; D018390:Gene Targeting; D005921:Glomerulonephritis / Q000209:etiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006706:Homeostasis; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2