BCL-6 PROTEIN IS EXPRESSED IN GERMINAL-CENTER B-CELLS
BCL-6 PROTEIN IS EXPRESSED IN GERMINAL-CENTER B-CELLS
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DOI：
10.1182/blood.v86.1.45.bloodjournal86145
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发表时间：
1995-07-01
期刊：
影响因子：
20.3
通讯作者：
DALLAFAVERA, R
中科院分区：
文献类型：
--
作者：
CATTORETTI, G;CHANG, CC;DALLAFAVERA, R
在40%的弥漫性大细胞淋巴瘤（DLCL）和5% - 10%的滤泡性淋巴瘤（FL）中发现了BCL - 6基因5'非编码区的结构改变，这表明BCL - 6表达失调可能在淋巴瘤发生中起作用。BCL - 6 cDNA的核苷酸测序预测出一种含有六个锌指结构域的蛋白质，这表明它可能作为一种转录因子发挥作用。本研究利用针对N端和C端BCL - 6合成寡肽产生的抗血清，通过免疫沉淀、免疫印迹和免疫细胞化学分析，将BCL - 6基因产物鉴定为一种95 - kD的核蛋白。对代表各种造血谱系/分化阶段的人类肿瘤细胞系进行的蛋白质印迹分析表明，BCL - 6蛋白主要在B细胞谱系中表达，在成熟B细胞中可检测到。对正常人淋巴组织进行的免疫组织化学分析表明，BCL - 6的表达在空间上局限于生发中心，包括所有的中心母细胞和中心细胞。在滤泡间和滤泡内的CD4(+)T细胞中也可检测到BCL - 6蛋白，但在其他滤泡成分中，包括套区B细胞、浆细胞、树突状细胞和巨噬细胞中则检测不到。对DLCL和FL活检样本进行的免疫组织化学分析表明，无论是否存在BCL - 6基因重排，在这些肿瘤中都可检测到BCL - 6蛋白。这些结果表明，BCL - 6基因的表达在B细胞分化过程中受到特异性调控，并提示BCL - 6在生发中心的发育或功能中起作用。由于DLCL来源于生发中心B细胞，BCL - 6表达失调可能通过阻止生发中心后的分化而促进淋巴瘤的发生。（C）1995年，美国血液学会。
Structural alterations of the 5' noncoding region of the BCL-6 gene have been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 10% of follicular lymphomas (FL), suggesting that deregulated BCL-6 expression may play a role in lymphomagenesis. Nucleotide sequencing of BCL-6 cDNA predicted a protein containing six zinc-finger domains, suggesting that it may function as a transcription factor. Using antisera raised against N- and C-terminal BCL-6 synthetic oligopeptides in immunoprecipitation, immunoblot, and immunocytochemical assays, this study identifies the BCL-6 gene product as a 95-kD nuclear protein, Western blot analysis of human tumor cell lines representative of various hematopoietic lineages/stages of differentiation showed that the BCL-6 protein is predominantly expressed in the B-cell lineage where it was found in mature B cells, Immunohistochemical analysis of normal human lymphoid tissues indicated that BCL-6 expression is topographically restricted to germinal centers including all centroblasts and centrocytes. The BCL-6 protein was also detectable in inter- and intrafollicular CD4(+) T cells, but not in other follicular components including mantle-zone B cells, plasma cells, dendritic cells, and macrophages. Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements. These results indicate that the expression of the BCL-6 gene is specifically regulated during B-cell differentiation and suggest a role for BCL-6 in germinal center development or function. Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation. (C) 1995 by The American Society of Hematology.