Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1
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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Some reports have revealed positive effects in overexpressing XBP-1, a transcription factor regulating the unfolded protein response during ER stress.
“Some reports have revealed positive effects in overexpressing XBP-1 (X-box binding protein 1), a transcription factor regulating the unfolded protein response (UPR) during ER stress (Iwakoshi et al., 2003;Tigges and Fussenegger, 2006;Becker et al., 2008;Ku et al., 2008).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Iwakoshi et al., 2003
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- Authors
- Iwakoshi, N. N., Lee, A.-H., Vallabhajosyula, P., Otipoby, K. L., Rajewsky, K., & Glimcher, L. H.
- Affiliations
- Harvard University (US)
- Corresponding author
- Glimcher, Laurie H.
- Venue
- Nature Immunology
- Published
- 2003-03-03
- Volume
- 4
- Issue
- 4
- Pages
- 321-329
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2025846979
- Cited by
- 880
- References
- 3
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 21 · 2023: 25 · 2022: 26 · 2021: 38 · 2020: 30 · 2019: 40 · 2018: 33 · 2017: 28 · 2016: 37 · 2015: 40 · 2014: 50 · 2013: 46 · 2012: 58
- FWCI
- 13.85
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-04-10)
- Open access
- closed
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- XBP1, unfolded protein response, plasma cell differentiation, IRE1, XBP1 splicing, antibody production, B cells, IL-4, interleukin-6, plasma cell survival, transcription factors
- MeSH terms
- Regulatory Factor X Transcription Factors, X-Box Binding Protein 1, Animals, B-Lymphocytes, Cell Differentiation, DNA-Binding Proteins, Immunoglobulin M, Immunoglobulin Heavy Chains, Plasma Cells, RNA Splicing, Transcription Factors, Interleukin-4, Interleukin-6, Protein Folding, Mice
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