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

Author

Listed:
  • Brian T. Gaudette

    (Perelman School of Medicine at the University of Pennsylvania)

  • Derek D. Jones

    (Perelman School of Medicine at the University of Pennsylvania)

  • Alexandra Bortnick

    (Perelman School of Medicine at the University of Pennsylvania)

  • Yair Argon

    (Perelman School of Medicine at the University of Pennsylvania
    The Children’s Hospital of Philadelphia)

  • David Allman

    (Perelman School of Medicine at the University of Pennsylvania)

Abstract

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.

Suggested Citation

  • Brian T. Gaudette & Derek D. Jones & Alexandra Bortnick & Yair Argon & David Allman, 2020. "mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14032-1
    DOI: 10.1038/s41467-019-14032-1
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    Cited by:

    1. Davide G. Franchina & Henry Kurniawan & Melanie Grusdat & Carole Binsfeld & Luana Guerra & Lynn Bonetti & Leticia Soriano-Baguet & Anouk Ewen & Takumi Kobayashi & Sophie Farinelle & Anna Rita Minafra , 2022. "Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Fiamma Salerno & Andrew J. M. Howden & Louise S. Matheson & Özge Gizlenci & Michael Screen & Holger Lingel & Monika C. Brunner-Weinzierl & Martin Turner, 2023. "An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Clara Cousu & Eléonore Mulot & Annie Smet & Sara Formichetti & Damiana Lecoeuche & Jianke Ren & Kathrin Muegge & Matthieu Boulard & Jean-Claude Weill & Claude-Agnès Reynaud & Sébastien Storck, 2023. "Germinal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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