Increased mTOR cancels out the effect of reduced Xbp-1 on antibody secretion in IL-1α-deficient B cells

Cell Immunol. 2018 Jun:328:9-17. doi: 10.1016/j.cellimm.2018.02.015. Epub 2018 Feb 24.

Abstract

IL-1α in vitro promotes immunoglobulin secretion by inducing proliferation of mature B cells, whereas IL-1α deficiency has no effect on in vivo antibody production. However, the reason IL-1α deficiency does not reduce in vivo antibody production is still unclear. In this study, we found that similar as in vivo data, IL-1α deficiency did not affect antibody production in in vitro LPS-stimulated B cells. Surprisingly, LPS-stimulated IL-1α-/- B cells reduced a key antibody production-related transcription factor X-box binding protein 1 (Xbp-1) expression. Furthermore, we found that IL-1α deficiency up-regulated mTOR expression, which bypassed Xbp-1 for immunoglobulin secretion. Finally, we showed that Xbp-1 suppressed mTOR expression, whereas mTOR suppressed the activation of Xbp-1 promoter via JunB. Together, these data suggest that IL-1a deficiency reduced Xbp-1 and up-regulated mTOR. This may explain why IL-1α deficiency has no effect on antibody production.

Keywords: Antibody; B cells; IL-1α; Xbp-1; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression Regulation / immunology
  • Interleukin-1alpha / immunology
  • Interleukin-1alpha / metabolism
  • Interleukin-1alpha / physiology
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plasma Cells / immunology
  • Protein Transport
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / physiology*
  • Transcription Factors / genetics
  • Transcriptional Activation
  • X-Box Binding Protein 1 / genetics
  • X-Box Binding Protein 1 / immunology
  • X-Box Binding Protein 1 / metabolism*

Substances

  • DNA-Binding Proteins
  • IL1A protein, human
  • Interleukin-1alpha
  • Lipopolysaccharides
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases