Identification of genes encoding critical factors regulating B-cell terminal differentiation in torafugu (Takifugu rubripes)
Identification of genes encoding critical factors regulating B-cell terminal differentiation in torafugu (Takifugu rubripes)
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DOI：
10.1016/j.cbd.2005.10.003
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发表时间：
2006-03-01
影响因子：
3
通讯作者：
Hiroishi, Shingo
中科院分区：
文献类型：
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作者：
Ohtani, Maki;Miyadai, Toshiaki;Hiroishi, Shingo
许多转录因子和相关辅助因子参与哺乳动物 B 细胞终末分化的调节。在硬骨鱼和软骨鱼中，尽管有证据强烈表明存在B细胞样淋巴细胞，但B细胞终末分化的机制仍有待阐明。在本研究中，我们使用河豚BLAST服务器搜索与促进B细胞终末分化的关键调节因子相似的核苷酸和氨基酸序列。我们从红鳍东方鲀中克隆了以下cDNA：（1）B淋巴细胞诱导成熟蛋白-1（Blimp-1），它通过抑制许多参与维持成熟B细胞分化的基因的转录，在促进浆细胞分化中发挥重要作用； (2) Bcl-6，促进生发中心形成并抑制Blimp-1表达； (3) X-box 结合蛋白-1 (XBP-1)，它通过激活 ER 应激相关基因的转录来控制 Ig 分泌； (4) Pax-5，它抑制 XBP-1 并增强激活诱导的胞苷脱氨酶 (AID) 的表达，AID 是免疫球蛋白基因体细胞连字章和类别转换重组的诱导剂； (5) TLE-3，Groucho 家族蛋白之一，Blimp-1 的辅助因子。我们还通过计算机和/或 cDNA 克隆鉴定了 Blimp-1 的其他辅助因子和许多靶基因。这些发现表明鱼类 B 细胞终末分化的基本过程受与哺乳动物相同的因素控制。 (c) 2005 Elsevier Inc. 保留所有权利。
Many transcription factors, and associated co-factors, are involved in the regulation of B-cell terminal differentiation in mammals. In the teleost and cartilaginous fish, although evidence has strongly suggested the existence of B-cell like lymphocytes, the mechanism of terminal differentiation of B-cells remains to be elucidated. In the present study, we searched for the nucleotide and amino acid sequences similar to the critical regulatory factors facilitating the terminal differentiation of B-cells using the fugu BLAST server. We cloned the following cDNAs from Takifugu rubripes: (1) B-lymphocyte-induced maturation protein-1 (Blimp-1), which plays a major role in promoting plasma cell differentiation by repressing the transcription of many genes that participate in maintaining the differentiation of mature B-cells; (2) BcI-6, which facilitates germinal center formation and represses Blimp-1 expression; (3) X-box binding protein-1 (XBP-1), which operates Ig secretion by activating transcription of the ER-stress responsible genes; (4) Pax-5, which suppresses XBP-1 and enhances the expression of activation-induced cytidine deaminase (AID), an inducer of somatic hypen-nutation and class-switch recombination of the immunoglobulin gene; and (5) TLE-3, one of the Groucho family proteins, a co-factor for Blimp-1. We also identified other co-factors and many target genes of Blimp-1 by in silico and/or cDNA cloning. These finding indicates that the basal process of B-cell terminal differentiation in fish is controlled by factors identical to those in mammals. (c) 2005 Elsevier Inc. All rights reserved.