{"doi":"10.3389/fimmu.2022.909475","title":"B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis","abstract":"Immunoglobulin M (IgM) to oxidation specific epitopes (OSE) are inversely associated with atherosclerosis in mice and humans. The B-1b subtype of B-1 cells secrete IgM to OSE, and unlike B-1a cells, are capable of long-lasting IgM memory. What attributes make B-1b cells different than B-1a cells is unknown. Our objectives were to determine how B-1b cells produce more IgM compared to B-1a cells at homeostatic condition and to see the differences in the B-1a and B-1b cell distribution and IgM CDR-H3 sequences in mice with advanced atherosclerosis. Here, in-vivo studies demonstrated greater migration to spleen, splenic production of IgM and plasma IgM levels in ApoE -/- Rag1 -/- mice intraperitoneally injected with equal numbers of B-1b compared to B-1a cells. Bulk RNA seq analysis and flow cytometry of B-1a and B-1b cells identified CCR6 as a chemokine receptor more highly expressed on B-1b cells compared to B-1a. Knockout of CCR6 resulted in reduced B-1b cell migration to the spleen. Moreover, B-1b cell numbers were significantly higher in spleen of aged atherosclerotic ApoE -/- mice compared to young ApoE -/- mice. Single cell sequencing results of IgHM in B-1a and B-1b cells from peritoneal cavity and spleen of atherosclerotic aged ApoE -/- mice revealed significantly more N additions at the V-D and D-J junctions, greater diversity in V region usage and CDR-H3 sequences in B-1b compared to B-1a cells. In summary, B-1b cells demonstrated enhanced CCR6-mediated splenic migration, IgM production, and IgM repertoire diversification compared to B-1a cells. These findings suggest that potential strategies to selectively augment B-1b cell numbers and splenic trafficking could lead to increased and more diverse IgM targeting OSE to limit atherosclerosis.","journal":"Frontiers in Immunology","year":2022,"id":271928,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":495595,"name":"Tanyaporn Pattarabanjird","orcid":"0000-0003-0994-1491","position":1,"is_corresponding":false},{"id":818034,"name":"Aditi Upadhye","orcid":"0000-0001-7204-6276","position":2,"is_corresponding":false},{"id":312150,"name":"Sai Vineela Bontha","orcid":"0000-0001-8914-1966","position":3,"is_corresponding":false},{"id":917481,"name":"Victoria Osinski","orcid":"0000-0002-8969-8454","position":4,"is_corresponding":false},{"id":710945,"name":"Melissa A. Marshall","orcid":null,"position":5,"is_corresponding":false},{"id":710378,"name":"James C. Garmey","orcid":"0000-0001-7456-8617","position":6,"is_corresponding":false},{"id":937782,"name":"Justine Deroissart","orcid":"0000-0003-0042-8712","position":7,"is_corresponding":false},{"id":895164,"name":"Thomas A Prohaska","orcid":"0000-0002-1406-692X","position":8,"is_corresponding":false},{"id":228443,"name":"Joseph L. Witztum","orcid":"0000-0002-5195-6614","position":9,"is_corresponding":false},{"id":530254,"name":"Christoph J. Binder","orcid":"0000-0001-8313-7050","position":10,"is_corresponding":false},{"id":933759,"name":"Nichol E. Holodick","orcid":"0000-0002-2671-6918","position":11,"is_corresponding":false},{"id":770129,"name":"Thomas L. Rothstein","orcid":"0009-0009-1589-1014","position":12,"is_corresponding":false},{"id":363873,"name":"Coleen A. McNamara","orcid":"0000-0002-0049-9986","position":13,"is_corresponding":false},{"id":676755,"name":"Prasad Srikakulapu","orcid":"0000-0003-3428-4518","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T00:27:43.806977Z","pmid":"35935999","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":[]}