Apoptosis in the development and maintenance of the immune system

Nat Immunol. 2003 May;4(5):410-5. doi: 10.1038/ni0503-410.


Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death domain, designated the Bcl-2 homology 3 (BH3) domain. BH3-only proteins operate as upstream sentinels, selectively sensing both intrinsic and extrinsic death stimuli. They communicate this information to the pro-apoptotic 'multidomain' members Bax or Bak--a process that is antagonized by anti-apoptotic members of the Bcl-2 family. The functional balance of pro-apoptotic versus anti-apoptotic influences, which operates at organelles, determines whether a lymphocyte will live or die. BH3-only molecules, often working in concert, compete for downstream multidomain pro- and anti-apoptotic BCL-2 members to control serial stages of lymphocyte development and homeostasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Caspases / immunology
  • Homeostasis
  • Humans
  • Immune System / cytology*
  • Immune System / growth & development
  • Mice
  • Models, Immunological
  • Proto-Oncogene Proteins c-bcl-2 / immunology


  • Proto-Oncogene Proteins c-bcl-2
  • Caspases