Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response
Jing Wang
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorGui-Xin Ruan
Department of Basic Medicine, School of Medicine, Taizhou University, Taizhou, China
Search for more papers by this authorYuxing Li
School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou, China
Search for more papers by this authorXiong Xiao
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorZhijian Zhu
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorWenjing Chen
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorHengjun Huang
Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, China
Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, China
Search for more papers by this authorRui Zhang
School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China
Search for more papers by this authorRuisi Wang
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorMeiyuan Chen
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorLing Guo
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorCorresponding Author
Yan Li
Shenzhen Hospital, Southern Medical University, Shenzhen, China
Search for more papers by this authorCorresponding Author
Shengli Xu
Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
Search for more papers by this authorCorresponding Author
Xijun Ou
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorJing Wang
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorGui-Xin Ruan
Department of Basic Medicine, School of Medicine, Taizhou University, Taizhou, China
Search for more papers by this authorYuxing Li
School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou, China
Search for more papers by this authorXiong Xiao
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorZhijian Zhu
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorWenjing Chen
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorHengjun Huang
Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, China
Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, China
Search for more papers by this authorRui Zhang
School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China
Search for more papers by this authorRuisi Wang
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorMeiyuan Chen
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorLing Guo
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorCorresponding Author
Yan Li
Shenzhen Hospital, Southern Medical University, Shenzhen, China
Search for more papers by this authorCorresponding Author
Shengli Xu
Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
Search for more papers by this authorCorresponding Author
Xijun Ou
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
Search for more papers by this authorFunding: The research was supported by the National Key R&D Program of China (2023YFA1800100 to X.O.), Shenzhen Fundamental Research Program (grant no. 20231120144916001, JCYJ20240813094400001, and JCYJ20220530115212028 to X.O.), National Natural Science Foundation of China (grant no. 32170882 and 32470938 to X.O.).
ABSTRACT
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.
Conflicts of Interest
The authors declare conflicts of interest.
Open Research
Data Availability Statement
RNA-seq data in this study have been deposited in the Sequence Read Archive (SRA) database with the accession number SRP528427. The remaining datasets generated in this study are available from the corresponding author upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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