{"doi":"10.1101/2025.08.15.666880","title":"Early, adjuvant-responsive epigenetic programs in B cells imprint subsequent plasma cell survival and the duration of humoral immunity","abstract":"ABSTRACT The duration of antibody production varies across different infections and vaccines. To define molecular programs that promote durable humoral immunity, we used mice deficient in ZBTB20, a transcription factor that is highly expressed by plasma cells and required to maintain antibody production in vivo . However, genetic deletion of Zbtb20 in long-lived plasma cells had no impact on the duration of antibody production. Instead, deletion of Zbtb20 in B cells only within the first week after immunization caused a subsequent failure to maintain plasma cells. Through single-cell ATAC-sequencing, we observed elevated IRF8- and Ets-dependent epigenetic programs in ZBTB20-deficient B cells at 7 days post-immunization. The corresponding transcriptional changes were observed ∼1 week later. Switching from alum to an oil-in-water adjuvant suppressed Ets-dependent epigenetic programs and rescued ZBTB20-deficient antibody responses. Deletion of Irf8 also rescued ZBTB20-deficient antibody responses. Thus, B cell-intrinsic epigenetic programs imprint durable antibody production at an early stage, prior to major transcriptional consequences and weeks before most long-lived plasma cells are formed.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572746,"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":0.956,"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":262620,"name":"Lucas J. D’Souza","orcid":"0000-0003-4132-7328","position":1,"is_corresponding":false},{"id":1197950,"name":"James F. Read","orcid":"0000-0003-2962-6835","position":2,"is_corresponding":false},{"id":1479334,"name":"Wenjie Qi","orcid":"0000-0001-9232-1407","position":3,"is_corresponding":false},{"id":94705,"name":"Darren A. Cusanovich","orcid":"0000-0001-6889-0095","position":4,"is_corresponding":false},{"id":242112,"name":"Stacey Schultz‐Cherry","orcid":"0000-0002-2021-727X","position":5,"is_corresponding":false},{"id":1479335,"name":"Lynn M. Corcoran","orcid":"0000-0003-4493-5011","position":6,"is_corresponding":false},{"id":1169068,"name":"Anthony Bosco","orcid":"0000-0002-4335-615X","position":7,"is_corresponding":false},{"id":231648,"name":"Deepta Bhattacharya","orcid":"0000-0001-8377-7699","position":8,"is_corresponding":false},{"id":231624,"name":"Tyler J. Ripperger","orcid":"0000-0003-1686-0147","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40894624","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":[]}