BCL-6 expression during B-cell activation
BCL-6 expression during B-cell activation
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DOI：
10.1182/blood.v87.12.5257.bloodjournal87125257
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发表时间：
1996-06-15
期刊：
影响因子：
20.3
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Allman, D;Jain, A;Staudt, LM
BCL-6基因易位在弥漫性大细胞型非霍奇金淋巴瘤中很常见，尽管BCL-6编码区是完整的，但其5'非翻译区被易位伴侣的序列所取代。本研究表明，BCL-6在淋巴细胞中的表达在促有丝分裂刺激过程中受到调节。静息B和T淋巴细胞含有高水平的BCL-6 mRNA。用抗IgM或IgD抗体、细菌脂多糖、佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素或CD 40配体刺激小鼠B细胞导致BCL-6 mRNA水平降低5倍至35倍。在用金黄色葡萄球菌加白细胞介素-2或抗IgM抗体刺激的人B细胞和用植物血凝素刺激的人T淋巴细胞中观察到类似的BCL-6 mRNA下调。BCL-6 mRNA水平在刺激后8 ~ 16小时开始下降，细胞进入S期之前。尽管体外多克隆活化B细胞总是降低BCL-6 mRNA的表达，但来自人生殖中心的活化B细胞表达的BCL-6 mRNA水平与静息B细胞中的水平相当。尽管有这些相似的mRNA水平，但在生发中心B细胞中BCL-6蛋白表达比在静息B细胞中高3倍至34倍，表明BCL-6蛋白水平受翻译或翻译后机制控制。这些观察结果表明生发中心反应向B细胞提供独特的激活信号，其允许持续的高水平BCL-6表达，（C）1996年由美国血液学学会。
Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma, Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner, The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA, Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a fivefold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 mRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms, These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression, (C) 1996 by The American Society of Hematology.