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

European Journal of Immunology

10.1002/eji.202451508

https://doi.org/10.1002/eji.202451508

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

04 April 2025

Wang, J., Ruan, G., Li, Y., Xiao, X., Zhu, Z., Chen, W., Huang, H., Zhang, R., Wang, R., Chen, M., Guo, L., Li, Y., Xu, S., & Ou, X. (2025). Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response. European Journal of Immunology, 55(4). Portico. https://doi.org/10.1002/eji.202451508

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.

Publisher Copyright

This research is supported by core funding from: Singapore Immunology Network (SIgN)
Grant Reference no. :

This is the peer reviewed version of the following article: Wang, J., Ruan, G., Li, Y., Xiao, X., Zhu, Z., Chen, W., Huang, H., Zhang, R., Wang, R., Chen, M., Guo, L., Li, Y., Xu, S., & Ou, X. (2025). Minor Splicing Factor RNPC3 Is Essential for the Germinal Center B Cell Response. European Journal of Immunology, 55(4). Portico. https://doi.org/10.1002/eji.202451508 , which has been published in final form at https://doi.org/10.1002/eji.202451508. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

https://oar.a-star.edu.sg/communities-collections/articles/23033

0014-2980
1521-4141

Singapore Immunology Network