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