Role of acetyl-CoA metabolism in B cell germinal center reaction

B cell development is characterized by both metabolic and epigenetic reprogramming. Notably, metabolic inputs can be integrated into the epigenome to inform cell fate decisions in physiological and pathological contexts. Nevertheless, it is still unclear how metabolic cues reshape B cell chromatin landscape. This study investigates the impact of acetyl-CoA metabolism on germinal center B cell specification. Glucose 13-CARBON tracing on ex vivo stimulated primary B cells reveals that acetyl-CoA de novo synthesis is augmented upon B cell stimulation with a cocktail mimicking the germinal center reaction (anti-IgM, anti-CD40 and IL-4). Stimulated B cells display increased levels of Histone H3 and H4 acetylation, while blockade of the reading of acetylated histones by JQ-1, a BET bromodomain proteins inhibitor, impairs differentiation towards the germinal center phenotype. In summary, this study demonstrates that metabolic-dependent histone acetylation guides germinal center B cell differentiation.