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Apoptosis in the development and maintenance of the immune system

Nature Immunology volume 4, pages 410–415 (2003)Cite this article

Abstract

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.

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Figure 1
Figure 2: Cell death pathways.
Figure 3: Detail of the mitochondrial apoptotic pathway.

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Acknowledgements

We thank E. D. Smith for figures.

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  1. Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, MA, USA

    Joseph T. Opferman & Stanley J. Korsmeyer

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Opferman, J., Korsmeyer, S. Apoptosis in the development and maintenance of the immune system. Nat Immunol 4, 410–415 (2003). https://doi.org/10.1038/ni0503-410

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