The Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Nat Commun. 2020 Feb 5;11(1):723. doi: 10.1038/s41467-019-14032-1.
How activated B cells build biosynthetic pathways and organelle structures necessary for subsequent robust antibody secretion is still unclear. The dominant model holds that nascent plasma cells adapt to increased antibody synthesis by activating the unfolded protein response (UPR) under the control of the transcription factor Xbp1. Here, by analyzing gene expression in activated B cells with or without plasma cell-inductive signals, we find that follicular B cells up-regulate a wide array of UPR-affiliated genes before initiating antibody secretion; furthermore, initial transcription of these loci requires the mTORC1 kinase adaptor, Raptor, but not Xbp1. Transcriptomic analyses of resting marginal zone B cells, which generate plasma cells with exceptionally rapid kinetics, reinforce these results by revealing the basal expression of UPR-affiliated mRNA networks without detectable Xbp1 activity. We thus conclude that B cells utilize mTORC1 to prepare for subsequent plasma cell function, before the onset of antibody synthesis.
尚不清楚活化 B 细胞如何构建生物合成途径和细胞器结构，这些结构对于随后的强效抗体分泌是必需的。主流模型认为，在转录因子 Xbp1 的控制下，新生成的浆细胞通过激活未折叠蛋白反应 (UPR) 来适应增加的抗体合成。在这里，通过分析有或没有浆细胞诱导信号的活化 B 细胞中的基因表达，我们发现滤泡 B 细胞在开始分泌抗体之前会上调广泛的 UPR 相关基因；此外，这些基因座的初始转录需要 mTORC1 激酶接头 Raptor，但不需要 Xbp1。对产生浆细胞动力学异常迅速的静止边缘区 B 细胞的转录组学分析通过揭示 UPR 相关 mRNA 网络的基础表达而没有检测到 Xbp1 活性，进一步证实了这些结果。因此，我们得出结论，B 细胞在开始合成抗体之前，利用 mTORC1 为随后的浆细胞功能做准备。
