{"doi":"10.1101/2025.09.01.673552","title":"CD11c+ Tbet+ B cells constrain obesity- and vaccination-induced germinal center B cells and T helper cells","abstract":"SUMMARY Obesity is a rapidly growing public health crisis associated simultaneously with increased metabolic disease and humoral immune suppression to vaccination or infection. 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 FH and hepatic CXCR5-T PH 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 FH , T PH 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":574242,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244479,"name":"Benjamin T. Enslow","orcid":"0000-0003-4822-0216","position":1,"is_corresponding":false},{"id":82382,"name":"Emma Collins","orcid":"0000-0003-3774-8189","position":2,"is_corresponding":false},{"id":1482037,"name":"Madilyn Dominguez-Lowry","orcid":null,"position":3,"is_corresponding":false},{"id":1150892,"name":"Nathaniel Liendo","orcid":"0000-0001-8708-681X","position":4,"is_corresponding":false},{"id":788531,"name":"Elizabeth Dudley","orcid":null,"position":5,"is_corresponding":false},{"id":378096,"name":"Elizabeth A. Leadbetter","orcid":"0000-0003-4994-6684","position":6,"is_corresponding":false},{"id":852937,"name":"Carlo Vanz","orcid":"0000-0002-3676-004X","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"40950217","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}