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k/vol1/fastq/SRR246/050/SRR24600350/SRR24600350_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/060/SRR24600360/SRR24600360_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/062/SRR24600362/SRR24600362_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/056/SRR24600356/SRR24600356_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/044/SRR24600344/SRR24600344_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/038/SRR24600338/SRR24600338_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/045/SRR24600345/SRR24600345_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/033/SRR24600333/SRR24600333_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/039/SRR24600339/SRR24600339_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR246/032/SRR24600332/SRR24600332_1.fastq.gzprimary200OKGenomicsMSKCChttps://www.ebi.ac.uk/ena/browser/view/PRJNA973112Mus musculusxref:PubMed:37365386Following 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: JH4 sequencing of LDHA-sufficient and -deficient splenocytesENAfalseHigh-throughput JH4 sequencing of germinal centers of LDHA-suffiicient and -deficient B cellsHigh-throughput JH4 sequencing of germinal centers of LDHA-suffiicient and -deficient B cells2025-09-242023-06-03PRJNA973112GSE2326581009037365386