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mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion

机译:MTORC1在前面的抗体分泌前的活化的B细胞中坐标坐标。在前面的抗体分泌中的活化B细胞中坐落于展开蛋白响应相关转录组

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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.
机译:如何激活B细胞构建后续稳健抗体分泌所需的生物合成途径和细胞器结构仍然不清楚。主导模型通过在转录因子XBP1的控制下激活展开的蛋白质反应(UPR)来保持新血浆细胞适应增加的抗体合成。这里,通过在具有或不含血浆细胞感应信号的活化B细胞中分析基因表达,我们发现卵泡B细胞在启动抗体分泌之前上调了各种UPR-隶属化基因;此外,这些基因座的初始转录需要MTORC1激酶适配器,猛禽,但不是XBP1。休息边际区B细胞的转录组分析,其产生具有异常快速动力学的血浆细胞,通过揭示UPR-隶属MRNA网络的基础表达而没有可检测的XBP1活性来加强这些结果。因此,我们得出结论,B细胞利用MTORC1准备在抗体合成开始之前的后续浆细胞功能。

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