GERMINAL CENTER CELLS EXPRESS BCL-2 PROTEIN AFTER ACTIVATION BY SIGNALS WHICH PREVENT THEIR ENTRY INTO APOPTOSIS
GERMINAL CENTER CELLS EXPRESS BCL-2 PROTEIN AFTER ACTIVATION BY SIGNALS WHICH PREVENT THEIR ENTRY INTO APOPTOSIS
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DOI：
10.1002/eji.1830210819
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发表时间：
1991-08-01
影响因子：
5.4
通讯作者：
MACLENNAN, ICM
中科院分区：
文献类型：
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作者：
LIU, YJ;MASON, DY;MACLENNAN, ICM
B细胞在生发中心内根据其被滤泡树突状细胞上的抗原激活的能力进行选择。在培养中分离的生发中心B细胞通过凋亡来杀死自己，但如果它们的抗原受体是交叉连接的，这一点就会被阻止。本研究证实，与其他B细胞不同，几乎所有的生发中心B细胞都不表达bcl2癌基因编码的25 kDa蛋白。分离的生发中心细胞表面Ig的交联会使它们表达bcl1蛋白。另外两种抑制生发中心细胞进入细胞凋亡的刺激可导致bcl2蛋白的表达。这些刺激物是：(A)CD40抗体和(B)CD23蛋白的重组25 kDa片段和重组白介素1-α。它们分别诱导生发中心细胞分化为静息B细胞或浆母细胞。对小淋巴细胞的双重荧光研究证实，线粒体中存在bcl2蛋白，但也存在于其他核外区域。Burkitt淋巴瘤细胞的表型表明，它们是起源于生发中心的肿瘤细胞。并对Burkitt淋巴瘤细胞系bcl2蛋白的表达进行了研究。保留新鲜Burkitt淋巴瘤细胞表型的Burkitt细胞系在钙离子载体离子霉素的作用下，可诱导其进入凋亡状态。这些细胞不表达bcl2蛋白。相反，已向淋巴母细胞系表型漂移的Burkitt细胞株则高水平表达bcl2蛋白。研究结果支持生发中心细胞进入凋亡的易感性与其缺乏bcl2蛋白表达有关的概念。某些肿瘤生发中心细胞bcl2蛋白的异常表达可能使其在正常生发中心细胞死亡的情况下存活。
B cells undergo selection within germinal centers on the basis of their capacity to be activated by antigen held on follicular dendritic cells. Isolated germinal center B cells in culture kill themselves by apoptosis but this is prevented if their receptors for antigen are cross-linked. In this study it is confirmed that almost all germinal center B cells, unlike other B cells, do not express the 25-kDa protein encoded by the bcl-2 oncogene. Cross-linking the surface Ig of isolated germinal center cells causes them to express bcl- protein. Two other stimuli which inhibit the entry of germinal center cells to apoptosis result in the expression of bcl-2 protein. These stimuli are: (a) CD40 antibody and (b) recombinant 25-kDa fragment of the CD23 protein plus recombinant interleukin 1-alpha. Respectively, these induce germinal center cells to differentiate to resting B cells or plasmablasts. Dual-fluorescence studies on small lymphocytes confirm the presence of bcl-2 protein in mitochondria but show that this is also present in other extra-nuclear areas.Burkitt lymphoma cells have a phenotype which indicates that they are neoplastic cells of germinal center origin. The expression of bcl-2 protein by Burkitt lymphoma lines was also studied. Burkitt lines which retain the phenotype of fresh Burkitt lymphoma cells can be induced to enter apoptosis on culture with the Ca2+ ionophore ionomycin. These cells were found not to express bcl-2 protein. By contrast, Burkitt lines which have drifted towards a lymphoblastoid cell line phenotype and are resistant to the induction of apoptosis express high levels of the bcl-2 protein.The findings support the concept that the susceptibility of germinal center cells to entering apoptosis is associated with their lack of expression of bcl-2 protein. Aberrant expression of bcl-2 protein by some neoplastic germinal center cells may allow survival in situations where their normal counterparts die.