BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
Author
Bouillet, P; Purton, JF; Godfrey, DI; Zhang, LC; Coultas, L; Puthalakath, H; Pellegrini, M; Cory, S; Adams, JM; Strasser, ADate
2002-02-21Source Title
NATUREPublisher
NATURE PUBLISHING GROUPAffiliation
Medical Biology (W.E.H.I.)Metadata
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Journal ArticleCitations
Bouillet, P., Purton, J. F., Godfrey, D. I., Zhang, L. C., Coultas, L., Puthalakath, H., Pellegrini, M., Cory, S., Adams, J. M. & Strasser, A. (2002). BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. NATURE, 415 (6874), pp.922-926. https://doi.org/10.1038/415922a.Access Status
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10.1038/415922aDescription
C1 - Journal Articles Refereed
Abstract
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.
Keywords
Cell Development (incl. Cell Division and Apoptosis) ; Genetic Immunology ; Cancer and Related DisordersExport Reference in RIS Format
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