RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center response[RNA-seq]
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. Overall design: To investigate the role of Pcbp1 in B cell development and function, we generated Pcbp1 floxed (fl/fl) Mb1-Cre mice (Pcbp1 BKO) and induced germinal center B cell differentiation using the 40-LB system (iGCB). We then conducted gene expression profiling analysis based on RNA-seq data obtained from naive B cells and iGCB cells. we performed a comparative gene expression profiling analysis of RNA-seq data for naive B cells (2 pairs of WT vs KO) and iGCB cells (3 pairs of WT vs KO).