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

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

Neal N Iwakoshi  1 , Ann-Hwee Lee, Prasanth Vallabhajosyula, Kevin L Otipoby, Klaus Rajewsky, Laurie H Glimcher
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Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1

Neal N Iwakoshi et al. Nat Immunol. 2003 Apr.

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Abstract

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.

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