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Regulation of hematopoiesis by the transcription factors Bach1 and Bach2

转录因子 Bach1 和 Bach2 调节造血作用

基本信息

批准号：
15390095
负责人：
IGARASHI Kazuhiko
金额：
$ 9.54万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390095/
关键词：
Bach1 Bach2 transcription factor globin B cell heme oxidative stress Maf

项目摘要

For the sake of clarity, I shall give a summary of the analysis of B cell system below.Activated B cells differentiate to plasma cells to secrete immunoglobulin MI (IgM) or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins. Diversification of antibody function by CSR is important for humoral immunity. However, it remains unclear how the decision for the bifurcation is made. Bach2 is a B cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only prior to plasma cell stage. Here we report that Bach2 is critical for CSR and somatic hypermutation (SHM) of immunoglobulin genes. Genetic ablation of bach2 in mice revealed that Bach2 was required for both T cell-independent and -dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM as did wild-type cells and expressed abundantly Blimp-1 and XBP-1, critical regulators of the plasmacytic differentiation, suggesting that Bach2 was not required for the plasmacytic differentiation per se. However, they failed to undergo efficient CSR. These findings define Bach2 as a key regulator of antibody response and provide an insight into the orchestration of CSR and SHM during plasma cell differentiation.

为了清楚起见，我将在下面给出对B细胞系统的分析的总结。活化的B细胞分化为浆细胞以分泌免疫球蛋白MI（IgM），或者在经历类别转换重组（CSR）之后，分泌其他类别的免疫球蛋白。通过CSR使抗体功能多样化对于体液免疫是重要的。然而，目前尚不清楚如何决定分叉。Bach 2是一种B细胞特异性转录抑制因子，与小Maf蛋白相互作用，小Maf蛋白仅在浆细胞阶段之前高表达。在这里，我们报告Bach 2是关键的CSR和体细胞超突变（SHM）的免疫球蛋白基因。在小鼠中对Bach 2的基因切除揭示了Bach 2对于T细胞非依赖性和依赖性IgG应答以及SHM都是必需的。当在体外刺激时，Bach 2缺陷型B细胞与野生型细胞一样产生IgM，并大量表达Blimp-1和XBP-1（浆细胞分化的关键调节因子），这表明Bach 2本身并不是浆细胞分化所需的。然而，他们没有进行有效的CSR。这些发现将Bach 2定义为抗体应答的关键调节因子，并提供了对浆细胞分化期间CSR和SHM的协调的见解。