The RNA-binding protein hnRNP F is required for the germinal center B cell response

The RNA-binding protein hnRNP F is required for the germinal center B cell response

Nature Communications

10.1038/s41467-023-37308-z

http://dx.doi.org/10.1038/s41467-023-37308-z

Hengjun Huang, Yuxing Li, Gaopu Zhang, Gui-Xin Ruan, Zhijian Zhu, Wenjing Chen, Jia Zou, Rui Zhang, Jing Wang, Yu Ouyang, Shengli Xu, Xijun Ou

General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry, Multidisciplinary

30 March 2023

Huang, H., Li, Y., Zhang, G., Ruan, G.-X., Zhu, Z., Chen, W., Zou, J., Zhang, R., Wang, J., Ouyang, Y., Xu, S., & Ou, X. (2023). The RNA-binding protein hnRNP F is required for the germinal center B cell response. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-37308-z

AbstractThe T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge. B cells deficient in hnRNP F are characterized by defective proliferation and c-Myc upregulation upon antigenic stimulation. Mechanistically, hnRNP F directly binds to the G-tracts of Cd40 pre-mRNA to promote the inclusion of Cd40 exon 6 that encodes its transmembrane domain, thus enabling appropriate CD40 cell surface expression. Furthermore, we find that hnRNP A1 and A2B1 can bind to the same region of Cd40 pre-mRNA but suppress exon 6 inclusion, suggesting that these hnRNPs and hnRNP F might antagonize each-other’s effects on Cd40 splicing. In summary, our study uncovers an important posttranscriptional mechanism regulating the GC response.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: 4 Singapore Immunology Network, Agency for Science, Technology and Research
Grant Reference no. : NA

https://oar.a-star.edu.sg/communities-collections/articles/19475

2041-1723

Singapore Immunology Network

https://doi.org/10.1038/s41467-023-37308-z