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

Neal N. Iwakoshi, Ann Hwee Lee, Prasanth Vallabhajosyula, Kevin L. Otipoby, Klaus Rajewsky, Laurie H. Glimcher

Research output: Contribution to journalArticlepeer-review

730 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalNature immunology
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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