{"doi":"10.3389/fimmu.2024.1380641","title":"Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity","abstract":"Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b). Consistent with this finding, circulating IgM, but not IgG, was elevated in TET2-KO mice compared to WT. Analysis of bulk RNASeq of sort purified peritoneal B-1a and B-1b cells revealed reduced expression of heavy and light chain immunoglobulin genes, predominantly in B-1a cells from TET2-KO mice compared to WT controls. As expected, the expression of IgM transcripts was the most abundant isotype in B-1 cells. Yet, only in B-1a cells there was a significant increase in the proportion of IgM transcripts in TET2-KO mice compared to WT. Analysis of the CDR3 of the BCR revealed an increased abundance of replicated CDR3 sequences in B-1 cells from TET2-KO mice, which was more clearly pronounced in B-1a compared to B-1b cells. V-D-J usage and circos plot analysis of V-J combinations showed enhanced usage of V H 11 and V H 12 pairings. Taken together, our study is the first to demonstrate that global loss of TET2 increases B-1 cell number and IgM production and reduces CDR3 diversity, which could impact many biological processes and disease states that are regulated by IgM.","journal":"Frontiers in Immunology","year":2024,"id":476541,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":833106,"name":"Maria Murach","orcid":"0000-0001-8994-2202","position":1,"is_corresponding":false},{"id":370033,"name":"Cassidy M.R. Blackburn","orcid":"0000-0002-6589-5349","position":2,"is_corresponding":false},{"id":710945,"name":"Melissa A. Marshall","orcid":null,"position":3,"is_corresponding":false},{"id":1314485,"name":"Katherine Root","orcid":null,"position":4,"is_corresponding":false},{"id":495595,"name":"Tanyaporn Pattarabanjird","orcid":"0000-0003-0994-1491","position":5,"is_corresponding":false},{"id":937782,"name":"Justine Deroissart","orcid":"0000-0003-0042-8712","position":6,"is_corresponding":false},{"id":362437,"name":"Loren D. Erickson","orcid":"0000-0001-6762-4625","position":7,"is_corresponding":false},{"id":530254,"name":"Christoph J. Binder","orcid":"0000-0001-8313-7050","position":8,"is_corresponding":false},{"id":392952,"name":"Stefan Bekiranov","orcid":"0000-0002-3177-4346","position":9,"is_corresponding":false},{"id":363873,"name":"Coleen A. McNamara","orcid":"0000-0002-0049-9986","position":10,"is_corresponding":false},{"id":908051,"name":"Emily Jane Dennis","orcid":"0000-0002-9858-7190","position":0,"is_corresponding":true}],"reference_count":129,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:29.605760Z","pmid":"38601144","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":[]}