Non‐homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double‐strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA‐PKcs, Artemis, PAXX, MRI) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

中文翻译：

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B和T淋巴细胞发育过程中非同源末端连接因子之间的遗传相互作用：体内小鼠模型。

非同源末端连接（NHEJ）是在整个细胞周期过程中修复双链断裂（DSB）的主要DNA修复机制。在V（D）J重组期间，发育中的B和T淋巴细胞中会产生DSB，以增加B和T细胞受体的组成。在类开关重组（CSR）过程中，在成熟的B淋巴细胞中也会生成DSB，从而提供抗体重链恒定区的独特效应子功能。因此，NHEJ对于V（D）J重组和CSR都是重要的。NHEJ由形成Ku异二聚体的核心Ku70和Ku80亚基组成，该亚二聚体结合DSB并促进募集辅助因子（例如DNA-PKcs，Artemis，PAXX，MRI）和下游核心因子（XLF，Lig4和XRCC4）。最近几十年来，已经报道了新的NHEJ蛋白，这种分子途径的复杂性不断增加。众多已经建立了体内小鼠模型，并对其进行了表征，以鉴定NHEJ因子的相互作用及其在适应性免疫系统发育中的作用。这篇综述总结了缺乏一个或几个NHEJ因素的当前可用的小鼠模型，特别关注早期B细胞的发育。我们还强调了小鼠NHEJ途径中的遗传相互作用和冗余。