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Regulation of Lymphoid Apoptosis by Bcl-2 and Bcl-xL

  • Gabriel Nuñez
  • Ramon Merino
  • Philip L. Simonian
  • Didier A. M. Grillot
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

Naturally occurring cell death is common during lymphoid development and activation. The death of developing lymphoid cells is a highly regulated process that serves to select lymphoid populations that are functionally competent, and to remove cells that are not longer needed or potentially autoreactivel. Elimination of self-reactive B and T lymphocytes by apoptosis is thought to play a major role in the establishment of self-tolerance. The latter process is mediated by high avidity interactions between antigen receptors and self-antigens2. In contrast, signaling via the Fas receptor appears to play a major role in the elimination of activated lymphocytes during immune responses in peripheral tissues3. In addition, to the antigen and Fas receptors, survival of lymphocytes is controlled by certain cytokines and costimulatory signals4−5. The intracellular mechanism that regulates and executes the death program is still poorly understood but it is thought that cell death is controlled by a genetic program induced within the dying lymphocyte. Recently, several genes have been identified that appear to play critical roles in lymphoid survival6. The bc1-2 protooncogene was the first member of a growing family of genes that suppresses cell death in lymphoid cells7. Constitutive expression of bc1-2 in lymphoid cells prevents or delays apoptosis induced by multiple stimuli7. A role of Bc1-2 in T and B-cell biology was suggested by its highly restricted cellular distribution during development and in mature lymphoid populations8−9. Recent evidences suggest that Bc1-2 plays a role in positive selection of thymocytes 10−12. However, the ability of Bc1-2 to influence negative selection of thymocytes and immature B cells is controversial13−15.

Keywords

Lymphoid Cell Negative Selection Transgenic Animal Antigen Receptor Clonal Deletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Gabriel Nuñez
    • 1
  • Ramon Merino
    • 1
  • Philip L. Simonian
    • 1
  • Didier A. M. Grillot
    • 1
  1. 1.Department of PathologyThe University of Michigan Medical SchoolAnn ArborUSA

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