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RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE275669 | GEO | 2024/08/31

REPOSITORIES: GEO

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RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[scRNA-seq]

Project description: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.

2024-08-31 | GSE275672 | GEO

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RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[scRNA-seq]

Project description:RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[scRNA-seq]

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RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[RNA-seq]

Project description:RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[RNA-seq]

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Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation

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