The transcriptional programme of antibody class switching involves the repressor Bach2
The transcriptional programme of antibody class switching involves the repressor Bach2
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DOI：
10.1038/nature02596
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发表时间：
2004-06-03
期刊：
影响因子：
64.8
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Muto, A;Tashiro, S;Igarashi, K
活化的B细胞分化为浆细胞以分泌IgM，或在经历类别转换重组（CSR）后分泌其他类别的免疫球蛋白（1-4）。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，其仅在浆细胞阶段之前高表达（5-7）。在这里，我们表明Bach 2对免疫球蛋白基因的CSR和体细胞超突变（SHM）（2，4，8）至关重要。小鼠Bach 2的基因消除揭示了Bach 2是T细胞非依赖性和T细胞依赖性IgG应答和SHM所必需的。当在体外刺激时，Bach 2缺陷型B细胞产生IgM，野生型细胞也是如此，并大量表达Blimp-1（参考文献9，10）和XBP-1（参考文献11），这是浆细胞分化的关键调节因子（12），表明Bach 2本身不是浆细胞分化所必需的。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。
Activated B cells differentiate to plasma cells to secrete IgM or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins(1-4). 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 before the plasma cell stage(5-7). Here we show that Bach2 is critical for CSR and somatic hypermutation (SHM)(2,4,8) of immunoglobulin genes. Genetic ablation of Bach2 in mice revealed that Bach2 was required for both T-cell-independent and T-cell-dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM, as did wild-type cells, and abundantly expressed Blimp-1 (refs 9, 10) and XBP-1 (ref. 11), critical regulators of the plasmacytic differentiation(12), indicating that Bach2 was not required for the plasmacytic differentiation itself. 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.