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dc.contributor.authorBouillet, P
dc.contributor.authorPurton, JF
dc.contributor.authorGodfrey, DI
dc.contributor.authorZhang, LC
dc.contributor.authorCoultas, L
dc.contributor.authorPuthalakath, H
dc.contributor.authorPellegrini, M
dc.contributor.authorCory, S
dc.contributor.authorAdams, JM
dc.contributor.authorStrasser, A
dc.date.available2014-05-21T19:29:55Z
dc.date.issued2002-02-21
dc.identifierpii: 415922a
dc.identifier.citationBouillet, 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.
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/11343/26373
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractDuring 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.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.subjectCell Development (incl. Cell Division and Apoptosis) ; Genetic Immunology ; Cancer and Related Disorders
dc.titleBH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
dc.typeJournal Article
dc.identifier.doi10.1038/415922a
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleNATURE
melbourne.source.volume415
melbourne.source.issue6874
melbourne.source.pages922-926
melbourne.publicationid17602
melbourne.elementsid256718
melbourne.contributor.authorGodfrey, Dale
melbourne.contributor.authorCory, Suzanne
melbourne.contributor.authorCOULTAS, LEIGH
melbourne.contributor.authorBouillet, Philippe
dc.identifier.eissn1476-4687
melbourne.accessrightsThis item is currently not available from this repository


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