Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1

Nat Immunol. 2003 Apr;4(4):321-9. doi: 10.1038/ni907. Epub 2003 Mar 3.


The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, providing an integral link between XBP-1, the UPR and plasma cell differentiation. Signals involved in plasma cell differentiation, specifically interleukin-4, control the transcription of XBP-1, whereas its post-transcriptional processing is dependent on synthesis of immunoglobulins during B cell differentiation. We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Mice
  • Plasma Cells / cytology
  • Plasma Cells / physiology*
  • Protein Folding
  • RNA Splicing / physiology
  • Regulatory Factor X Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*
  • X-Box Binding Protein 1


  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Interleukin-6
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Interleukin-4