RNA binding protein Pcbp1 maintains mitochondria integrity to promote antibody production and germinal center...

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 immunoglobulin M expression at steady state and compromised differentiation of germinal center B cells and production of high-affinity antibodies upon immunization. These effects were caused by defective mitochondrial integrity in Pcbp1-deficient B cells, including impaired mitochondrial electron transport chain complex I and elevated mitochondrial reactive oxygen species production. Mechanistically, Pcbp1 binds to the 3' untranslated region of Fdxr messenger RNA to promote its expression, thereby supporting iron-sulfur cluster biogenesis, the assembly of mitochondrial complex I, and other Fdxr-dependent processes. Our findings reveal a previously unidentified role for Pcbp1 in regulating mitochondrial function, protein synthesis, and antibody responses in B cells, providing insight into posttranscriptional regulation and mitochondrial functions in adaptive immunity.