Choi M S, Boise L H, Gottschalk A R, Quintans J, Thompson C B, Klaus G G
National Institute for Medical Research, Mill Hill, London, GB.
Eur J Immunol. 1995 May;25(5):1352-7. doi: 10.1002/eji.1830250533.
The phenotypically immature B cell lymphoma WEHI-231 undergoes apoptotic cell death when cultured with anti-immunoglobulin (Ig) antibodies, via a bcl-2-independent mechanism. We have therefore studied the role of the bcl-2-related protein bcl-x in controlling cell death in WEHI-231. We find that overexpression of the long form of bcl-x (bcl-XL) renders these cells refractory to anti-Ig-induced cell death. Stimulation of WEHI-231 via CD40 has similar protective effects. We show here that ligation of CD40 rapidly induces the appearance of the bcl-XL protein in WEHI-231, while stimulation via sIgM, sIgD, CD5 or CD45 receptors, or with phorbol esters plus ionomycin does not. WEHI-231 cells also rapidly undergo massive apoptosis following culture with thapsigargin, a specific inhibitor of the Ca(2+)-ATPase of the endoplasmic reticulum: this is also reversed by anti-CD40, or by overexpression of bcl-XL. We, therefore, conclude that bcl-XL plays a key role in the regulation of antigen receptor-mediated apoptosis via CD40 in WEHI-231. In addition, the fact that this protein is not induced in WEHI-231 in response to phorbol dibutyrate plus ionomycin points to a fundamental signaling defect in these cells, which could conceivably be a reflection of their immature, apoptosis-susceptible phenotype.
表型未成熟的B细胞淋巴瘤WEHI-231在用抗免疫球蛋白（Ig）抗体培养时，通过一种不依赖bcl-2的机制发生凋亡性细胞死亡。因此，我们研究了bcl-2相关蛋白bcl-x在控制WEHI-231细胞死亡中的作用。我们发现，bcl-x长形式（bcl-XL）的过表达使这些细胞对抗Ig诱导的细胞死亡具有抗性。通过CD40刺激WEHI-231具有类似的保护作用。我们在此表明，CD40的连接迅速诱导WEHI-231中bcl-XL蛋白的出现，而通过sIgM、sIgD、CD5或CD45受体刺激，或用佛波酯加离子霉素刺激则不会。在用毒胡萝卜素（一种内质网Ca(2+)-ATP酶的特异性抑制剂）培养后，WEHI-231细胞也会迅速发生大量凋亡：抗CD40或bcl-XL的过表达也可逆转这种凋亡。因此，我们得出结论，bcl-XL在通过CD40调节WEHI-231中抗原受体介导的凋亡中起关键作用。此外，在WEHI-231中，这种蛋白不会因佛波二丁酸酯加离子霉素而被诱导，这一事实表明这些细胞存在基本的信号缺陷，这可能反映了它们未成熟、易发生凋亡的表型。
