{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sharma R"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS"],"pagination":["1358-1369"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11262065"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(8)"],"pubmed_abstract":["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-specific and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a bacterial lipopolysaccharide-induced extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in their 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."],"journal":["Nature immunology"],"pubmed_title":["Distinct metabolic requirements regulate B cell activation and germinal center responses."],"pmcid":["PMC11262065"],"funding_grant_id":["U54CA137788","P30 CA008748","R01AI072194","P30CA008748","R01 AI072194","AI 102888","R01 AI102888","U54 CA137788","R25 AI140472","AI140472","R01 AI124186"],"pubmed_authors":["Cross JR","Cols M","Sharma R","Smolkin RM","Hu W","Alread W","Violante S","Yen WF","Chaudhuri J","Chowdhury P","Wang ZM","Fernandez KC","Chaligne R","Kim Y","Li MO"],"additional_accession":[]},"is_claimable":false,"name":"Distinct metabolic requirements regulate B cell activation and germinal center responses.","description":"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-specific and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a bacterial lipopolysaccharide-induced extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in their 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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2025-04-04T14:46:12.665Z","creation":"2025-04-04T14:46:12.665Z"},"accession":"S-EPMC11262065","cross_references":{"pubmed":["37365386"],"doi":["10.1038/s41590-023-01540-y"]}}