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BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes 总被引:41,自引:0,他引:41
Bouillet P Purton JF Godfrey DI Zhang LC Coultas L Puthalakath H Pellegrini M Cory S Adams JM Strasser A 《Nature》2002,415(6874):922-926
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. 相似文献
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M. D. Purton 《Cellular and molecular life sciences : CMLS》1976,32(6):737-740
Summary Ultrastructural studies of the perisinusoidal space in the avian liver have demonstrated the presence of 2 extravascular cell types—a fat-storing cell and a free mesenchyme cell or histiocyte. This latter cell type is capable of participating in the formation of a bile canaliculus with the hepatic parenchymal cell. The possibility of the fatstoring cell differentiating from the histiocyte is suggested. 相似文献
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Brooker RA Du Z Blundy JD Kelley SP Allan NL Wood BJ Chamorro EM Wartho JA Purton JA 《Nature》2003,423(6941):738-741
Noble-gas geochemistry is an important tool for understanding planetary processes from accretion to mantle dynamics and atmospheric formation. Central to much of the modelling of such processes is the crystal-melt partitioning of noble gases during mantle melting, magma ascent and near-surface degassing. Geochemists have traditionally considered the 'inert' noble gases to be extremely incompatible elements, with almost 100 per cent extraction efficiency from the solid phase during melting processes. Previously published experimental data on partitioning between crystalline silicates and melts has, however, suggested that noble gases approach compatible behaviour, and a significant proportion should therefore remain in the mantle during melt extraction. Here we present experimental data to show that noble gases are more incompatible than previously demonstrated, but not necessarily to the extent assumed or required by geochemical models. Independent atomistic computer simulations indicate that noble gases can be considered as species of 'zero charge' incorporated at crystal lattice sites. Together with the lattice strain model, this provides a theoretical framework with which to model noble-gas geochemistry as a function of residual mantle mineralogy. 相似文献
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