• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes.

During lymphocyte development, the assembly of genes coding for antigen receptors occurs by the combinatorial linking of gene segments. The stochastic nature of this process gives rise to lymphocytes that can recognize self-antigens, thereby having the potential to induce autoimmune disease. Such autoreactive lymphocytes can be silenced by developmental arrest or unresponsiveness (anergy), or can be deleted from the repertoire by cell death. In the thymus, developing T lymphocytes (thymocytes) bearing a T-cell receptor (TCR)-CD3 complex that engages self-antigens are induced to undergo programmed cell death (apoptosis), but the mechanisms ensuring this 'negative selection' are unclear. We now report that thymocytes lacking the pro-apoptotic Bcl-2 family member Bim (also known as Bcl2l11) are refractory to apoptosis induced by TCR-CD3 stimulation. Moreover, in transgenic mice expressing autoreactive TCRs that provoke widespread deletion, Bim deficiency severely impaired thymocyte killing. TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection.

Pubmed ID: 11859372


  • Bouillet P
  • Purton JF
  • Godfrey DI
  • Zhang LC
  • Coultas L
  • Puthalakath H
  • Pellegrini M
  • Cory S
  • Adams JM
  • Strasser A



Publication Data

February 21, 2002

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD4
  • Antigens, CD8
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cells, Cultured
  • Enterotoxins
  • Female
  • Leukopoiesis
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein Transport
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Self Tolerance
  • Staphylococcus
  • Superantigens
  • T-Lymphocytes
  • Thymus Gland
  • bcl-X Protein