Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease.
B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX and BAK are essential for regulating the number of B cells at both immature and mature developmental stages. BAX and BAK are critical mediators of B cell death induced by multiple stimuli. In addition, BAX- and BAK-deficient B cells display defective cell cycle progression to B cell receptor crosslinking and lipopolysaccharide, but not to CpG-DNA. Furthermore, inducible deletion of Bax and Bak in adult mice results in the development of severe autoimmune disease.
Takeuchi
Osamu
O
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. otake@biken.osaka-u.ac.jp
Fisher
Jill
J
Suh
Heikyung
H
Harada
Hisashi
H
Malynn
Barbara A
BA
Korsmeyer
Stanley J
SJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11; D005434:Flow Cytometry; D005452:Fluoresceins; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D013388:Succinimides; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000276:immunology*
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D051017:Apoptosis Regulatory Proteins; C494773:Bak1 protein, mouse; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D005452:Fluoresceins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D013388:Succinimides; D050998:bcl-2 Homologous Antagonist-Killer Protein