{"title":"次要剪接因子RNPC3对生发中心B细胞应答至关重要","authors":"Jing Wang, Gui-Xin Ruan, Yuxing Li, Xiong Xiao, Zhijian Zhu, Wenjing Chen, Hengjun Huang, Rui Zhang, Ruisi Wang, Meiyuan Chen, Ling Guo, Yan Li, Shengli Xu, Xijun Ou","doi":"10.1002/eji.202451508","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Germinal center (GC) response ensures the generation of diverse and high-affinity antibodies during the T cell-dependent (TD) immune response. This process is controlled by coordinated transcriptional and posttranscriptional gene regulatory mechanisms. Minor intron splicing is known to be involved in posttranscriptional regulation of gene expression. RNA-binding region (RNP1, RRM) containing 3 (RNPC3) is a minor spliceosome component involved in stabilizing the U11/U12 di-snRNP complex, which is essential for minor intron splicing. However, it remains unclear if RNPC3 and RNPC3-related gene regulatory mechanisms are important for the TD immune response. In this study, we conditionally ablated RNPC3 in activated B cells and showed that the mutant mice had defective antibody generation due to impaired GC B cell response. We demonstrate that RNPC3 deficiency inhibits the proliferation and promotes the apoptosis of activated B cells. Mechanistically, we show that RNPC3 regulates the development of GC B cells in a minor spliceosome-dependent manner by controlling the removal of minor introns from minor intron-containing genes associated with cell proliferation and apoptosis. Our study thus uncovers a previously unappreciated role for RNPC3 in regulating GC B cell response.</p>\n </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 4","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response\",\"authors\":\"Jing Wang, Gui-Xin Ruan, Yuxing Li, Xiong Xiao, Zhijian Zhu, Wenjing Chen, Hengjun Huang, Rui Zhang, Ruisi Wang, Meiyuan Chen, Ling Guo, Yan Li, Shengli Xu, Xijun Ou\",\"doi\":\"10.1002/eji.202451508\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Germinal center (GC) response ensures the generation of diverse and high-affinity antibodies during the T cell-dependent (TD) immune response. This process is controlled by coordinated transcriptional and posttranscriptional gene regulatory mechanisms. Minor intron splicing is known to be involved in posttranscriptional regulation of gene expression. RNA-binding region (RNP1, RRM) containing 3 (RNPC3) is a minor spliceosome component involved in stabilizing the U11/U12 di-snRNP complex, which is essential for minor intron splicing. However, it remains unclear if RNPC3 and RNPC3-related gene regulatory mechanisms are important for the TD immune response. In this study, we conditionally ablated RNPC3 in activated B cells and showed that the mutant mice had defective antibody generation due to impaired GC B cell response. We demonstrate that RNPC3 deficiency inhibits the proliferation and promotes the apoptosis of activated B cells. Mechanistically, we show that RNPC3 regulates the development of GC B cells in a minor spliceosome-dependent manner by controlling the removal of minor introns from minor intron-containing genes associated with cell proliferation and apoptosis. Our study thus uncovers a previously unappreciated role for RNPC3 in regulating GC B cell response.</p>\\n </div>\",\"PeriodicalId\":165,\"journal\":{\"name\":\"European Journal of Immunology\",\"volume\":\"55 4\",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451508\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451508","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response
Germinal center (GC) response ensures the generation of diverse and high-affinity antibodies during the T cell-dependent (TD) immune response. This process is controlled by coordinated transcriptional and posttranscriptional gene regulatory mechanisms. Minor intron splicing is known to be involved in posttranscriptional regulation of gene expression. RNA-binding region (RNP1, RRM) containing 3 (RNPC3) is a minor spliceosome component involved in stabilizing the U11/U12 di-snRNP complex, which is essential for minor intron splicing. However, it remains unclear if RNPC3 and RNPC3-related gene regulatory mechanisms are important for the TD immune response. In this study, we conditionally ablated RNPC3 in activated B cells and showed that the mutant mice had defective antibody generation due to impaired GC B cell response. We demonstrate that RNPC3 deficiency inhibits the proliferation and promotes the apoptosis of activated B cells. Mechanistically, we show that RNPC3 regulates the development of GC B cells in a minor spliceosome-dependent manner by controlling the removal of minor introns from minor intron-containing genes associated with cell proliferation and apoptosis. Our study thus uncovers a previously unappreciated role for RNPC3 in regulating GC B cell response.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.