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

First Author  Gaudette BT Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  723
PubMed ID  32024827 Mgi Jnum  J:287400
Mgi Id  MGI:6401734 Doi  10.1038/s41467-019-14032-1
Citation  Gaudette BT, et al. (2020) mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion. Nat Commun 11(1):723
abstractText  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.
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