生发中心B细胞在缺氧微环境中以极高速率进行增殖，但推动这一过程的细胞过程尚不完全清楚。在这里，我们展示了生发中心B细胞的线粒体高度动态，具有显著升高的转录和翻译速率，与转录因子A、线粒体（TFAM）的活性有关。TFAM在正常B细胞发育中也是必需的，对于活化的生发中心前体B细胞进入生发中心反应很重要，Tfam的缺失显著损害了生发中心的形成、功能和产物。B细胞中TFAM的丧失会破坏肌动蛋白细胞骨架，并抑制生发中心B细胞响应于趋化因子信号的细胞活动力，导致它们空间的错乱。我们展示了B细胞淋巴瘤显著增加线粒体翻译，并且在c-Myc转基因小鼠模型中，B细胞中Tfam的缺失可抗击淋巴瘤的发展。最后，我们展示了线粒体转录和翻译的药理抑制可抑制人类淋巴瘤细胞的生长，引发肌动蛋白细胞骨架的类似缺陷。© 2023. 版权所有，南方都市报社，未经授权禁止转载。

Germinal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor A, mitochondrial (TFAM). TFAM, while also necessary for normal B cell development, is required for entry of activated GC precursor B cells into the germinal center reaction; deletion of Tfam significantly impairs GC formation, function and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signaling, leading to their spatial disorganization. We show that B cell lymphoma substantially increases mitochondrial translation and that deletion of Tfam in B cells is protective against the development of lymphoma in a c-Myc transgenic mouse model. Finally, we show that pharmacological inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells and induces similar defects in the actin cytoskeleton.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.