次要剪接因子RNPC3对生发中心B细胞应答至关重要

IF 4.5 3区 医学 Q2 IMMUNOLOGY
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
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引用次数: 0

摘要

生发中心(GC)反应确保在T细胞依赖性(TD)免疫反应中产生多样化和高亲和力的抗体。这个过程是由协调的转录和转录后基因调控机制控制的。已知次要内含子剪接参与基因表达的转录后调控。含有3 (RNPC3)的rna结合区(RNP1, RRM)是一种次要剪接体成分,参与稳定U11/U12 di-snRNP复合物,这是次要内含子剪接所必需的。然而,RNPC3和RNPC3相关基因调控机制在TD免疫应答中是否重要尚不清楚。在这项研究中,我们在活化的B细胞中有条件地消融RNPC3,并发现突变小鼠由于GC B细胞反应受损而产生抗体缺陷。我们证明RNPC3缺失抑制活化B细胞的增殖并促进其凋亡。在机制上,我们发现RNPC3通过控制从与细胞增殖和凋亡相关的含内含子的次要基因中去除次要内含子,以一种次要剪接体依赖的方式调节GC B细胞的发育。因此,我们的研究揭示了RNPC3在调节GC B细胞反应中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response

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.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
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.
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