Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1
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 −...
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| Veröffentlicht in: | Nature immunology 2003-04, Vol.4 (4), p.321-329 |
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| creator | Iwakoshi, Neal N. Lee, Ann-Hwee Vallabhajosyula, Prasanth Otipoby, Kevin L. Rajewsky, Klaus Glimcher, Laurie H. |
| description | 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. |
| doi_str_mv | 10.1038/ni907 |
| format | Article |
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−/−
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.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni907</identifier><identifier>PMID: 12612580</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Activating transcription factor 1 ; Animals ; B-Lymphocytes - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cell differentiation ; Cell Differentiation - physiology ; Cell survival ; Coagulation factors ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - immunology ; DNA-Binding Proteins - metabolism ; Endonuclease ; Immunoglobulin Heavy Chains - biosynthesis ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Heavy Chains - immunology ; Immunoglobulin M - biosynthesis ; Immunoglobulin M - genetics ; Immunoglobulin M - immunology ; Immunoglobulins ; Immunology ; Infectious Diseases ; Interleukin 4 ; Interleukin 6 ; Interleukin-4 - metabolism ; Interleukin-6 - metabolism ; Lymphocytes B ; Mice ; Plasma cells ; Plasma Cells - cytology ; Plasma Cells - physiology ; Post-transcription ; Protein Folding ; Regulatory Factor X Transcription Factors ; RNA Splicing - physiology ; Transcription Factors - genetics ; Transcription Factors - immunology ; Transcription Factors - metabolism ; Upstream ; X-Box Binding Protein 1</subject><ispartof>Nature immunology, 2003-04, Vol.4 (4), p.321-329</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2003</rights><rights>Springer Nature America, Inc. 2003.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-f66a3b6bcb587b0be6b126a48eba48c6db8665c849bf1f46641c6130411f52bb3</citedby><cites>FETCH-LOGICAL-c461t-f66a3b6bcb587b0be6b126a48eba48c6db8665c849bf1f46641c6130411f52bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ni907$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni907$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12612580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwakoshi, Neal N.</creatorcontrib><creatorcontrib>Lee, Ann-Hwee</creatorcontrib><creatorcontrib>Vallabhajosyula, Prasanth</creatorcontrib><creatorcontrib>Otipoby, Kevin L.</creatorcontrib><creatorcontrib>Rajewsky, Klaus</creatorcontrib><creatorcontrib>Glimcher, Laurie H.</creatorcontrib><title>Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>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.</description><subject>Activating transcription factor 1</subject><subject>Animals</subject><subject>B-Lymphocytes - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - physiology</subject><subject>Cell survival</subject><subject>Coagulation factors</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - immunology</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endonuclease</subject><subject>Immunoglobulin Heavy Chains - biosynthesis</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - immunology</subject><subject>Immunoglobulin M - biosynthesis</subject><subject>Immunoglobulin M - genetics</subject><subject>Immunoglobulin M - immunology</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Interleukin 4</subject><subject>Interleukin 6</subject><subject>Interleukin-4 - 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Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwakoshi, Neal N.</au><au>Lee, Ann-Hwee</au><au>Vallabhajosyula, Prasanth</au><au>Otipoby, Kevin L.</au><au>Rajewsky, Klaus</au><au>Glimcher, Laurie H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>4</volume><issue>4</issue><spage>321</spage><epage>329</epage><pages>321-329</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12612580</pmid><doi>10.1038/ni907</doi><tpages>9</tpages></addata></record> |
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| ispartof | Nature immunology, 2003-04, Vol.4 (4), p.321-329 |
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| subjects | Activating transcription factor 1 Animals B-Lymphocytes - metabolism Biomedical and Life Sciences Biomedicine Cell differentiation Cell Differentiation - physiology Cell survival Coagulation factors DNA-Binding Proteins - genetics DNA-Binding Proteins - immunology DNA-Binding Proteins - metabolism Endonuclease Immunoglobulin Heavy Chains - biosynthesis Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin M - biosynthesis Immunoglobulin M - genetics Immunoglobulin M - immunology Immunoglobulins Immunology Infectious Diseases Interleukin 4 Interleukin 6 Interleukin-4 - metabolism Interleukin-6 - metabolism Lymphocytes B Mice Plasma cells Plasma Cells - cytology Plasma Cells - physiology Post-transcription Protein Folding Regulatory Factor X Transcription Factors RNA Splicing - physiology Transcription Factors - genetics Transcription Factors - immunology Transcription Factors - metabolism Upstream X-Box Binding Protein 1 |
| title | Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1 |
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