{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:10:07Z","timestamp":1789161007439,"version":"build-2803163510"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI128901"],"award-info":[{"award-number":["R01 AI128901"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The activation of lymphocytes in patients with lupus and in mouse models of the disease is coupled with an increased cellular metabolism in which glucose plays a major role. The pharmacological inhibition of glycolysis with 2-deoxy-d-glucose (2DG) reversed the expansion of follicular helper CD4+ T cells and germinal center B cells in lupus-prone mice, as well as the production of autoantibodies. The response of foreign Ags was however not affected by 2DG in these mice, suggesting that B and CD4+ T cell activation by autoantigens is uniquely sensitive to glycolysis. In this study, we tested this hypothesis with monoclonal B cells and CD4+ T cells specific for lupus-relevant autoantigens. AM14 V\u03ba8R (AM14) transgenic B cells are activated by IgG2a\/chromatin immune complexes and they can receive cognate help from chromatin-specific 13C2 CD4+ T cells. We showed that activation of AM14 B cells by their cognate Ag PL2-3 induced glycolysis, and that the inhibition of glycolysis reduced their activation and differentiation into Ab-forming cells, in the absence or presence of T cell help. The dependency of autoreactive B cells on glycolysis is in sharp contrast with the previously reported dependency of 4-hydroxy-3-nitrophenyl acetyl\u2013specific B cells on fatty acid oxidation. Contrary to AM14 B cells, the activation and differentiation of 13C2 T cells into follicular helper CD4+ T cells was not altered by 2DG, which differs from polyclonal CD4+ T cells from lupus-prone mice. These results further define the role of glycolysis in the production of lupus autoantibodies and demonstrate the need to evaluate the metabolic requirements of Ag-specific B and T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.2200325","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:23:36Z","timestamp":1672935816000},"page":"377-388","source":"Crossref","is-referenced-by-count":17,"title":["Glucose Requirement of Antigen-Specific Autoreactive B Cells and CD4+ T Cells"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-2515","authenticated-orcid":false,"given":"Georges","family":"Abboud","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-5983","authenticated-orcid":false,"given":"Yuk Pheel","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilani","family":"Zeumer-Spataro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Terrell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-9607","authenticated-orcid":false,"given":"Kirsten","family":"N\u00fcndel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"2025021007593815200_r1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3389\/fimmu.2018.00427","article-title":"Plasma cell differentiation pathways in systemic lupus erythematosus","volume":"9","author":"Malkiel","year":"2018","journal-title":"Front. 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