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

Hengjun Huang, Yuxing Li, Gaopu Zhang, Gui-Xin Ruan, Zhijian Zhu, Wenjing Chen, Jia Zou, Rui Zhang, Jing Wang, Yu Ouyang, Shengli Xu () and Xijun Ou ()
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Hengjun Huang: Southern University of Science and Technology
Yuxing Li: Southern University of Science and Technology
Gaopu Zhang: Southern University of Science and Technology
Gui-Xin Ruan: Taizhou University
Zhijian Zhu: Southern University of Science and Technology
Wenjing Chen: Southern University of Science and Technology
Jia Zou: Southern University of Science and Technology
Rui Zhang: Southern University of Science and Technology
Jing Wang: Southern University of Science and Technology
Yu Ouyang: Southern University of Science and Technology
Shengli Xu: Agency for Science, Technology and Research
Xijun Ou: Southern University of Science and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract The 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.

Date: 2023
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DOI: 10.1038/s41467-023-37308-z

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