XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells
XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2012
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| Online Access: | http://hdl.handle.net/1721.1/74263 https://orcid.org/0000-0003-0921-3144 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826214217789734912 |
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| author | Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Ploegh, Hidde Love, John C |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Ploegh, Hidde Love, John C |
| author_sort | Hu, Chih-Chi Andrew |
| collection | MIT |
| description | XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. |
| first_indexed | 2024-09-23T16:01:38Z |
| format | Article |
| id | mit-1721.1/74263 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:01:38Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/742632022-10-02T05:46:54Z XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Ploegh, Hidde Love, John C Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Whitehead Institute for Biomedical Research Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Love, J. Christopher Ploegh, Hidde XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. National Science Foundation (U.S.). Graduate Research Fellowship Program Cancer Research Institute (New York, N.Y.) (Fellowship) 2012-10-25T20:20:49Z 2012-10-25T20:20:49Z 2009-04 2009-02 Article http://purl.org/eprint/type/JournalArticle 0261-4189 1460-2075 http://hdl.handle.net/1721.1/74263 Hu, Chih-Chi Andrew et al. “XBP-1 Regulates Signal Transduction, Transcription Factors and Bone Marrow Colonization in B Cells.” The EMBO Journal 28.11 (2009): 1624–1636. © 2012 European Molecular Biology Organization https://orcid.org/0000-0003-0921-3144 https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1038/emboj.2009.117 EMBO Journal Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Hu, Chih-Chi Andrew Dougan, Stephanie K. McGehee, Annette M. Ploegh, Hidde Love, John C XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title_full | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title_fullStr | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title_full_unstemmed | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title_short | XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells |
| title_sort | xbp 1 regulates signal transduction transcription factors and bone marrow colonization in b cells |
| url | http://hdl.handle.net/1721.1/74263 https://orcid.org/0000-0003-0921-3144 https://orcid.org/0000-0002-1090-6071 |
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