Cutting Edge: The Transcription Factor Sox2 Regulates AID Expression in Class-Switched B Cells.
Cutting Edge: The Transcription Factor Sox2 Regulates AID Expression in Class-Switched B Cells.
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DOI：
10.4049/jimmunol.1502266
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发表时间：
2017-03-15
期刊：
影响因子：
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通讯作者：
Chaudhuri J
中科院分区：
文献类型：
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作者：
DiMenna LJ;Yen WF;Nicolas L;Sharma R;Saldanha ZN;Chaudhuri J
免疫球蛋白重链(IgH)类开关重组(CSR)是通过故意将AID诱导的DNA双链断裂(DSB)引入IgH基因座而发生的。由于DSB通常具有很高的毒性，调节AID表达的机制与CSR和基因组完整性都有很大的相关性；然而，这种调节过程的效应者仍然知之甚少。在这里，我们发现转录因子Sox2在活化的B细胞中表达，但几乎只在经历了CSR的B细胞中表达。我们证明，Sox2在脾B细胞中的强制表达严重抑制了AID的表达和CSR，而Sox2的缺失增加了IgH；c-Myc易位的频率。这些结果表明，Sox2可能调节类转换B细胞中AID的表达，以抑制与CSR相关的基因组不稳定性。
Immunoglobulin heavy chain (IgH) class switch recombination (CSR) occurs through the deliberate introduction of AID-instigated DNA double strand breaks (DSBs) into the IgH loci. Since DSBs are generally highly toxic, mechanisms that regulate AID expression are of much relevance to both CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. Here we show that the transcription factor Sox2 is expressed in activated B cells but almost exclusively in those that have undergone CSR. We demonstrate that enforced expression of Sox2 in splenic B cells severely inhibits AID expression and CSR, while deletion of Sox2 increases the frequency of IgH;c-Myc translocations. These results suggest that Sox2 may regulate AID expression in class-switched B cells to suppress genomic instability associated with CSR.