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| Status |
Public on Aug 31, 2024 |
| Title |
RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
B cells are crucial for adaptive immunity, orchestrating humoral responses by producing antibodies essential for pathogen clearance. Here, we show that Poly(rC) binding protein 1 (Pcbp1), a multifunctional RNA-binding protein, is a key regulator of antibody production in B cells. Pcbp1 deficiency in B cells resulted in significant reductions in IgM expression at steady state and compromised differentiation of germinal center B cells and production of high-affinity antibodies upon immunization. These effects result from compromised mitochondrial integrity in Pcbp1-deficient B cells, including compromised mitochondrial electron transport chain (ETC) complex I and increased mitochondrial ROS production. Blocking mitochondrial ROS production rescued IgM production and improved germinal center responses caused by Pcbp1 deficiency. Mechanistically, Pcbp1 promotes the expression of Fdxr, a critical component of ETC complex I, via binding to its 3’UTR. Overall, our findings reveal a novel role for Pcbp1 in regulating mitochondrial function, protein synthesis, and antibody responses in B cells, providing novel insight into post-transcriptional regulation and mitochondrial functions.
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| Overall design |
To elucidate the mechanism of Pcbp1 regulation in GCB development, NP+ GCB cells (CD19+ B220+ NP+ GL7+ CD95+) were isolated from wild-type (WT) or Pcbp1 fl/fl AID-Cre mice (Pcbp1 GCB KO) and analyzed using single-cell RNA sequencing (scRNA-seq).
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| Contributor(s) |
Chang X, Zhu L, Li G, Ling L |
| Citation missing |
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| Submission date |
Aug 26, 2024 |
| Last update date |
Aug 31, 2024 |
| Contact name |
Xing Chang |
| E-mail(s) |
changxing@westlake.edu.cn
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| Phone |
057187920973
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| Organization name |
Westlake University
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| Department |
School of Life Sciences
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| Lab |
Immune Regulation and Human Diseases
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| Street address |
No.18 Shilongshan Road Cloud Town
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| City |
Xihu District, Hangzhou |
| State/province |
Zhejiang |
| ZIP/Postal code |
310024 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1152555 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE275672_RAW.tar |
102.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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