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

Nat Commun. 2020 Feb 5;11(1):723. doi: 10.1038/s41467-019-14032-1.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies / metabolism*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology*
  • Cell Differentiation
  • Gene Expression Regulation
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Regulatory-Associated Protein of mTOR / genetics
  • Regulatory-Associated Protein of mTOR / metabolism
  • Spleen / cytology
  • Unfolded Protein Response / genetics
  • Unfolded Protein Response / physiology*
  • X-Box Binding Protein 1 / genetics
  • X-Box Binding Protein 1 / metabolism

Substances

  • Antibodies
  • Lipopolysaccharides
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Mechanistic Target of Rapamycin Complex 1