Little is known about how cells regulate and integrate distinct biosynthetic pathways governing differentiation and cell division. For B lineage cells it is widely accepted that activated cells must complete several rounds of mitosis before yielding antibody-secreting plasma cells. However, we report that marginal zone (MZ) B cells, innate-like naive B cells known to generate plasma cells rapidly in response to blood-borne bacteria, generate functional plasma cells despite cell-cycle arrest. Further, short-term Notch2 blockade in vivo reversed division-independent differentiation potential and decreased transcript abundance for numerous mTORC1- and Myc-regulated genes. Myc loss compromised plasma cell differentiation for MZ B cells, and reciprocally induced ectopic mTORC1 signaling in follicular B cells enabled division-independent differentiation and plasma cell–affiliated gene expression. We conclude that ongoing in situ Notch2/mTORC1 signaling in MZ B cells establishes a unique cellular state that enables rapid division-independent plasma cell differentiation.

中文翻译：

---

静止的先天样 B 细胞利用持续的 Notch2/mTORC1 信号传导来实现快速且不依赖有丝分裂的浆细胞分化

关于细胞如何调节和整合控制分化和细胞分裂的不同生物合成途径知之甚少。对于 B 系细胞，普遍认为活化细胞必须完成几轮有丝分裂才能产生分泌抗体的浆细胞。然而，我们报告边缘区 (MZ) B 细胞，即已知可快速产生浆细胞以响应血源性细菌的先天样幼稚 B 细胞，尽管细胞周期停滞，仍会产生功能性浆细胞。此外，体内的短期 Notch2 阻断逆转了不依赖于分裂的分化潜能，并降低了许多 mTORC1 和 Myc 调节基因的转录本丰度。Myc 损失损害了 MZ B 细胞的浆细胞分化，并且在滤泡 B 细胞中相互诱导的异位 mTORC1 信号传导能够实现不依赖于分裂的分化和浆细胞相关基因的表达。我们得出结论，MZ B 细胞中正在进行的原位 Notch2/mTORC1 信号传导建立了一种独特的细胞状态，使浆细胞能够快速分化为独立于分裂的浆细胞。