Institut de Pharmacologie Et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UT3), CNRS UMR5089, 205 Route de Narbonne, BP 64182, 31077, Toulouse, France.
MOBIDIC, INSERM U1236, Université de Rennes 1, Rennes, France.
Sci Rep. 2024 Mar 28;14(1):7370. doi: 10.1038/s41598-024-57576-z.
Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to replace the initial IgM by another antibody class (IgG, IgE or IgA). CSR is preceded by transcription of the IgH constant genes and is controlled by the super-enhancer 3' regulatory region (3'RR) in an activation-specific manner. The 3'RR is composed of four enhancers (hs3a, hs1-2, hs3b and hs4). In mature B cells, 3'RR activity correlates with transcription of its enhancers. CSR can also occur in primary developing B cells though at low frequency, but in contrast to mature B cells, the transcriptional elements that regulate the process in developing B cells are ill-known. In particular, the role of the 3'RR in the control of constant genes' transcription and CSR has not been addressed. Here, by using a mouse line devoid of the 3'RR and a culture system that highly enriches in pro-B cells, we show that the 3'RR activity is indeed required for switch transcription and CSR, though its effect varies in an isotype-specific manner and correlates with transcription of hs4 enhancer only.
类别转换重组（CSR）通过使成熟 B 细胞用另一种抗体类别（IgG、IgE 或 IgA）替代初始 IgM，在适应性免疫反应中发挥重要作用。CSR 发生在 IgH 恒定基因转录之前，并以激活特异性方式由超级增强子 3'调控区（3'RR）控制。3'RR 由四个增强子（hs3a、hs1-2、hs3b 和 hs4）组成。在成熟 B 细胞中，3'RR 的活性与增强子的转录相关。尽管 CSR 也可以在初级发育的 B 细胞中发生，但频率较低，但与成熟 B 细胞不同，调节发育中的 B 细胞中该过程的转录元件尚不清楚。特别是，3'RR 在控制恒定基因转录和 CSR 中的作用尚未得到解决。在这里，我们使用缺乏 3'RR 的小鼠系和高度富集在前 B 细胞的培养系统，表明 3'RR 活性确实需要进行类别转换转录和 CSR，尽管其作用以同种型特异性方式变化，并且仅与 hs4 增强子的转录相关。
