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A role of Bcl6 in regulation of somatic hypermutation in the immunoglobulin gene

Bcl6 在免疫球蛋白基因体细胞超突变调节中的作用

基本信息

批准号：
18390149
负责人：
TOKUHISA Takeshi
金额：
$ 10.7万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390149/
关键词：
immunology target gene cancer genome gene regulation

项目摘要

Bcl6 is highly expressed in germinal center B cells and is essential for development of high affinity memory B cells. Bcl6 functions as a sequence specific transcriptional repressor by recruiting a histone deacetylase complex. However, a role for Bcl6 in induction of somatic hypermutation in germinal center B cells is not known. When we examined mutation frequencies in the Ig class-switch region and the c-myc region of IgG1 B cells derived from Bcl6-deficient mice, the frequencies in Bcl6-deficient IgG1 B cells were higher than those in wild type IgG1 B cells. These mutations were mainly generated by conversion of adenine to guanine. RNA-editing adenosine deaminase (ADAR) family converts adenosine of pre-mRNA into inosine, which is subsequently translated as guanosine, and ADAR1 mRNA among ADAR family was overexpressed in various cells from Bcl6-deficient mice. The promoter analysis revealed that ADAR1 is a molecular target of Bcl6. Furthermore, the exogenous ADAR1 increased frequency of point mutations from adenine to guanine in those regions of wild type IgG1 B cells. Since ADAR1 mRNA is detected in germinal center B cells in spite of high Bcl6 expression, ADAR1 may contribute adenine-targeted somatic hypermutation in germinal center B cells.

Bcl6在生发中心B细胞中高度表达，对高亲和记忆B细胞的发育至关重要。Bcl6通过募集组蛋白去乙酰化酶复合体作为序列特异性转录抑制因子发挥作用。然而，Bcl6在生发中心B细胞体细胞超突变诱导中的作用尚不清楚。当我们检测来自bcl6缺陷小鼠的IgG1 B细胞的Ig类开关区和c-myc区域的突变频率时，bcl6缺陷的IgG1 B细胞的频率高于野生型IgG1 B细胞。这些突变主要是由腺嘌呤转化为鸟嘌呤产生的。rna编辑腺苷脱氨酶（ADAR）家族将pre-mRNA中的腺苷转化为肌苷，肌苷随后被翻译为鸟苷，ADAR家族中的ADAR1 mRNA在bcl6缺陷小鼠的各种细胞中过表达。启动子分析显示ADAR1是Bcl6的分子靶点。此外，外源性ADAR1增加了野生型IgG1 B细胞这些区域从腺嘌呤到鸟嘌呤的点突变频率。由于尽管Bcl6高表达，但在生发中心B细胞中仍检测到ADAR1 mRNA，因此ADAR1可能导致了生发中心B细胞中腺嘌呤靶向的体细胞超突变。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A distinct role for lL-4 and lL-21 in their collaboration on proliferation and differentiation of activated B cells.

lL-4 和 lL-21 在活化 B 细胞的增殖和分化方面发挥着独特的作用。

DOI：
发表时间：
2008
期刊：
Immunobiol. (印刷中)
影响因子：
0
作者：
Saito;et al.
通讯作者：
et al.

A distinct role for IL-4 and IL-21 in their collaboration on proliferation and differentiation of activated B cells

IL-4 和 IL-21 在活化 B 细胞增殖和分化中的协同作用的独特作用

DOI：
发表时间：
2008
期刊：
Immunobiol. (in press)
影响因子：
0
作者：
Saito;T.;Kitayama;D.;Sakamoto;A.;Tsuruoka;N.;Arima;M.;Hatano;M.;Miyazaki;M.;and Tokuhisa;T.
通讯作者：
T.

Bc16 protects apoptosis of naive B cells stimulated with IL-21

Bc16 保护 IL-21 刺激的初始 B 细胞凋亡