Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease

Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11272-7. doi: 10.1073/pnas.0504783102. Epub 2005 Jul 29.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology*
  • Bcl-2-Like Protein 11
  • Flow Cytometry
  • Fluoresceins
  • Immunohistochemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Succinimides
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / immunology*

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Apoptosis Regulatory Proteins
  • Bak1 protein, mouse
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Fluoresceins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Succinimides
  • bcl-2 Homologous Antagonist-Killer Protein