UMR CNRS 7276, INSERM 1262 and Université de Limoges: Contrôle de la Réponse Immune B et des Lymphoproliférations, 2 Rue du Pr. Descottes, Limoges, France.
Front Immunol. 2022 Jun 24;13:877930. doi: 10.3389/fimmu.2022.877930. eCollection 2022.
B cells undergo genetic rearrangements at immunoglobulin gene () loci during B cell maturation. First recombination occurs during early B cell stages followed by class switch recombination (CSR) and somatic hypermutation (SHM) which occur during mature B cell stages. Given that RAG1/2 induces DNA double strand breaks (DSBs) during recombination and AID (Activation-Induced Deaminase) leads to DNA modifications (mutations during SHM or DNA DSBs during CSR), it is mandatory that rearrangements be tightly regulated to avoid any mutations or translocations within oncogenes. Ig loci contain various -regulatory elements that are involved in germline transcription, chromatin modifications or RAG/AID recruitment. -regulatory elements are increasingly recognized as being involved in nuclear positioning, heterochromatin addressing and chromosome loop regulation. In this review, we examined multiple data showing the critical interest of studying gene regulation at the whole nucleus scale. In this context, we highlighted the essential function of gene regulatory elements that now have to be considered as nuclear organizers in B lymphocytes.
B 细胞在成熟过程中经历免疫球蛋白基因()位点的遗传重排。首先,重组发生在早期 B 细胞阶段,随后是类别转换重组(CSR)和体细胞高频突变(SHM),这些发生在成熟 B 细胞阶段。鉴于 RAG1/2 在重组过程中诱导 DNA 双链断裂(DSBs),而 AID(激活诱导脱氨酶)导致 DNA 修饰(SHM 期间的突变或 CSR 期间的 DNA DSBs),因此必须严格调控重组,以避免原癌基因中的任何突变或易位。Ig 基因座包含各种 -调节元件,参与种系转录、染色质修饰或 RAG/AID 募集。-调节元件越来越被认为参与核定位、异染色质寻址和染色体环调节。在这篇综述中,我们检查了多项数据,这些数据表明研究整个核尺度上的基因调控具有重要意义。在这种情况下,我们强调了基因调节元件的重要功能,这些元件现在必须被视为 B 淋巴细胞中的核组织者。