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Inflammatory CD11c+T-bet+ B cells increase in spleen and adipose tissue during obesity and exacerbate metabolic dysfunction via antibodies. We now find that during obesity Tbet+ B cells also expand in the liver but not omentum or mesenteric fat. Obese mice also develop increased splenic CXCR5+ T\n                  <jats:sub>FH<\/jats:sub>\n                  and hepatic CXCR5-T\n                  <jats:sub>PH<\/jats:sub>\n                  cells which serve as likely partners for antigen-experienced MHC-II+ CD11c+ Tbet+ B cells. We also observed that antibodies in obese mice, previously found to contribute to metabolic disease, largely circulate as inflammatory autoantigen-bound immune complexes. Obese mice lacking T-bet in B cells also develop increased autoantibody titers and expanded splenic germinal center (GC) B and T helper cells. T-bet+ B cell-deficient mice make a similarly enhanced GC, T\n                  <jats:sub>FH<\/jats:sub>\n                  , T\n                  <jats:sub>PH<\/jats:sub>\n                  response to haptenated-protein vaccination with a corresponding increase in antibody affinity, although there is no additive effect of obesity. These results are consistent with GC inhibition by expanded CD11c+ B cells demonstrated by others to occur during autoimmunity, suggesting a broadly universal mechanism which may explain reduced humoral immunity and poor clinical outcomes following infection in patients with obesity and other forms of chronic inflammation.\n                <\/jats:p>","DOI":"10.1101\/2025.09.01.673552","type":"posted-content","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T16:25:23Z","timestamp":1757089523000},"source":"Crossref","is-referenced-by-count":0,"title":["CD11c+ Tbet+ B cells constrain obesity- and vaccination-induced germinal center B cells and T helper cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-004X","authenticated-orcid":false,"given":"Carlo","family":"Vanz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-0216","authenticated-orcid":false,"given":"Benjamin T.","family":"Enslow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madilyn","family":"Dominguez-Lowry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8708-681X","authenticated-orcid":false,"given":"Nathaniel","family":"Liendo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Dudley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4994-6684","authenticated-orcid":false,"given":"Elizabeth A.","family":"Leadbetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100611151380000_2025.09.01.673552v2.1","unstructured":"Health Risks (2012). 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