SRP438117 PRJNA973113 GSE232659 pre-GC and GC B cell scRNAseq Following infection or vaccination, activated B cells at extrafollicular sites or within germinal centers (GCs) undergo vigorous clonal proliferation. Proliferating lymphocytes have been shown to undertake lactate dehydrogenase A (LDHA)-dependent aerobic glycolysis; however, the specific role of this metabolic pathway in a B cell transitioning from a naïve to a highly proliferative, activated state remains poorly defined. Here, we deleted LDHA in a stage- and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a T cell-independent extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in the capacities to form GCs and mount GC-dependent antibody responses. In addition, loss of LDHA in T cells severely compromised B cell-dependent immune responses. Strikingly, when LDHA was deleted in activated, as opposed to naïve, B cells, there were only minimal effects on the GC reaction and in the generation of high-affinity antibodies. These findings strongly suggest that naïve and activated B cells have distinct metabolic requirements that are further regulated by niche and cellular interactions. Overall design: We performed scRNA sequencing to understand role of LDHA in the activation and proliferation of germinal center (GC) B cells. We combined this technology to HASH-sequencing in order to measure analyze LDHA-sufficient and -deficient GCs in triplicate and BCR sequencing to detect clonality and validate hypermutation in the early potential GC cells. GSE232659 pubmed 37365386 parent_bioproject PRJNA973107