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

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The RNA-binding protein hnRNP F is required for the germinal center B cell response
Title:
The RNA-binding protein hnRNP F is required for the germinal center B cell response
Journal Title:
Nature Communications
Publication Date:
30 March 2023
Citation:
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
Abstract:
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research is supported by core funding from: 4 Singapore Immunology Network, Agency for Science, Technology and Research
Grant Reference no. : NA
Description:
ISSN:
2041-1723