The LRF transcription factor regulates mature B cell development and the germinal center response in mice
B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therap...
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| Veröffentlicht in: | The Journal of clinical investigation 2011-07, Vol.121 (7), p.2583-2598 |
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| creator | Sakurai, Nagisa Maeda, Manami Lee, Sung-Uk Ishikawa, Yuichi Li, Min Williams, John C Wang, Lisheng Su, Leila Suzuki, Mai Saito, Toshiki I Chiba, Shigeru Casola, Stefano Yagita, Hideo Teruya-Feldstein, Julie Tsuzuki, Shinobu Bhatia, Ravi Maeda, Takahiro |
| description | B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies. |
| doi_str_mv | 10.1172/jci45682 |
| format | Article |
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Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci45682</identifier><identifier>PMID: 21646720</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Anemia ; Animals ; Antigens ; Autoimmune diseases ; B cells ; B-Lymphocytes - immunology ; B-Lymphocytes - physiology ; Biomedical research ; Cell Differentiation - immunology ; Cells ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - immunology ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - immunology ; Gene Expression Regulation ; Genes ; Genetic aspects ; Germinal Center - cytology ; Germinal Center - immunology ; Germinal Center - physiology ; Immune response ; Leukemia ; Lymphocytes ; Lymphoma ; Mice ; Mice, Knockout ; Microarray Analysis ; Models, Molecular ; Mutation ; Physiological aspects ; Protein Conformation ; Protein Multimerization ; Proteins ; Risk factors ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Spleen - cytology ; Transcription factors ; Transcription Factors - chemistry ; Transcription Factors - genetics ; Transcription Factors - immunology</subject><ispartof>The Journal of clinical investigation, 2011-07, Vol.121 (7), p.2583-2598</ispartof><rights>COPYRIGHT 2011 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jul 2011</rights><rights>Copyright © 2011, American Society for Clinical Investigation 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c668t-fb27b3fb4557fc570615f5ad4cf4dbc0efcd257f1b225da4d1cd3b296397a9883</citedby><cites>FETCH-LOGICAL-c668t-fb27b3fb4557fc570615f5ad4cf4dbc0efcd257f1b225da4d1cd3b296397a9883</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223838/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223838/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21646720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakurai, Nagisa</creatorcontrib><creatorcontrib>Maeda, Manami</creatorcontrib><creatorcontrib>Lee, Sung-Uk</creatorcontrib><creatorcontrib>Ishikawa, Yuichi</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Williams, John C</creatorcontrib><creatorcontrib>Wang, Lisheng</creatorcontrib><creatorcontrib>Su, Leila</creatorcontrib><creatorcontrib>Suzuki, Mai</creatorcontrib><creatorcontrib>Saito, Toshiki I</creatorcontrib><creatorcontrib>Chiba, Shigeru</creatorcontrib><creatorcontrib>Casola, Stefano</creatorcontrib><creatorcontrib>Yagita, Hideo</creatorcontrib><creatorcontrib>Teruya-Feldstein, Julie</creatorcontrib><creatorcontrib>Tsuzuki, Shinobu</creatorcontrib><creatorcontrib>Bhatia, Ravi</creatorcontrib><creatorcontrib>Maeda, Takahiro</creatorcontrib><title>The LRF transcription factor regulates mature B cell development and the germinal center response in mice</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.</description><subject>Anemia</subject><subject>Animals</subject><subject>Antigens</subject><subject>Autoimmune diseases</subject><subject>B cells</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - physiology</subject><subject>Biomedical research</subject><subject>Cell Differentiation - immunology</subject><subject>Cells</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - immunology</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - immunology</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Germinal Center - cytology</subject><subject>Germinal Center - immunology</subject><subject>Germinal Center - physiology</subject><subject>Immune response</subject><subject>Leukemia</subject><subject>Lymphocytes</subject><subject>Lymphoma</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microarray Analysis</subject><subject>Models, Molecular</subject><subject>Mutation</subject><subject>Physiological aspects</subject><subject>Protein Conformation</subject><subject>Protein Multimerization</subject><subject>Proteins</subject><subject>Risk factors</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Spleen - cytology</subject><subject>Transcription factors</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - immunology</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqN0luL1DAUB_Aiiruugp9AgoKXh665NL28COvg6sjAwrr6GtL0pJOhTWaTdNFvb-qsy47Mg_Sh0PzOP-nJybLnBJ8SUtH3G2UKXtb0QXZMOK_zmrL6YXaMMSV5U7H6KHsSwgZjUhS8eJwdUVIWZUXxcWau1oBWl-coemmD8mYbjbNISxWdRx76aZARAhplnDygj0jBMKAObmBw2xFsRNJ2KKaQHvxorBySsBHm2rB1NgAyFo1GwdPskZZDgGe375Ps-_mnq8WXfHXxebk4W-WqLOuY65ZWLdNtwXmlFa9wSbjmsiuULrpWYdCqo2mJtJTyThYdUR1raVOyppJNXbOT7MMudzu1I3TzabwcxNabUfpfwkkj9lesWYve3QhGU9fYHPDmNsC76wlCFKMJ829LC24Koq54RSlpaJIv_5EbN_nUgxnVmPGSz3GvdqiXAwhjtUu7qjlSnNGSUI4bzJLKD6geLKQjOgvapM97_vSAT08HqdkHC97tFSQT4Wfs5RSCWH67_H978WPfvr5n1yCHuA5umOYxCvvw7Q4q70LwoO-uhGAxT7H4ulj-meJEX9y_wjv4d2zZb-7j6cg</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Sakurai, Nagisa</creator><creator>Maeda, Manami</creator><creator>Lee, Sung-Uk</creator><creator>Ishikawa, Yuichi</creator><creator>Li, Min</creator><creator>Williams, John C</creator><creator>Wang, Lisheng</creator><creator>Su, Leila</creator><creator>Suzuki, Mai</creator><creator>Saito, Toshiki I</creator><creator>Chiba, Shigeru</creator><creator>Casola, Stefano</creator><creator>Yagita, Hideo</creator><creator>Teruya-Feldstein, Julie</creator><creator>Tsuzuki, Shinobu</creator><creator>Bhatia, Ravi</creator><creator>Maeda, Takahiro</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110701</creationdate><title>The LRF transcription factor regulates mature B cell development and the germinal center response in mice</title><author>Sakurai, Nagisa ; Maeda, Manami ; Lee, Sung-Uk ; Ishikawa, Yuichi ; Li, Min ; Williams, John C ; Wang, Lisheng ; Su, Leila ; Suzuki, Mai ; Saito, Toshiki I ; Chiba, Shigeru ; Casola, Stefano ; Yagita, Hideo ; Teruya-Feldstein, Julie ; Tsuzuki, Shinobu ; Bhatia, Ravi ; Maeda, Takahiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c668t-fb27b3fb4557fc570615f5ad4cf4dbc0efcd257f1b225da4d1cd3b296397a9883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anemia</topic><topic>Animals</topic><topic>Antigens</topic><topic>Autoimmune diseases</topic><topic>B cells</topic><topic>B-Lymphocytes - 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| source | MEDLINE; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Anemia Animals Antigens Autoimmune diseases B cells B-Lymphocytes - immunology B-Lymphocytes - physiology Biomedical research Cell Differentiation - immunology Cells Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - immunology DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics DNA-Binding Proteins - immunology Gene Expression Regulation Genes Genetic aspects Germinal Center - cytology Germinal Center - immunology Germinal Center - physiology Immune response Leukemia Lymphocytes Lymphoma Mice Mice, Knockout Microarray Analysis Models, Molecular Mutation Physiological aspects Protein Conformation Protein Multimerization Proteins Risk factors RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Spleen - cytology Transcription factors Transcription Factors - chemistry Transcription Factors - genetics Transcription Factors - immunology |
| title | The LRF transcription factor regulates mature B cell development and the germinal center response in mice |
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