{"doi":"10.3389/fcvm.2021.791028","title":"Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease","abstract":"Background: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive. Methods: Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP. Bioinformatics approaches were used to identify B cell subtype(s) and transcriptomic signatures associated with α-gal sensitization. In vitro characterization of chemokine/chemokine receptor pairs on switched memory B cells associated with IgE to α-gal was performed. Results: Of the 60 patients, 17 (28%) were positive for IgE to α-gal. CITESeq identified CCR6+ class-switched memory (SWM) B cells and CXCR4 expresssion on these CCR6+ SWM B cells as significantly associated with IgE sensitization to α-gal but not to other common allergens (peanut or inhalants). In vitro studies of enriched human B cells revealed significantly greater IgE on SWM B cells with high CCR6 and CXCR4 expression 10 days after cells were treated with IL-4 and CD40 to stimulate class switch recombination. Both CCL20 (CCR6 ligand) and CXCL12 (ligand for CXCR4) increased the expression of IgE on SWM B cells expressing their receptors. However, they appeared to have unique pathways mediating this effect as only CCL20 increased activation-induced cytidine deaminase (AID), while CXCL12 drove proliferation of CXCR4+ SWM B cells. Lastly, correlation analysis indicated an association between CAD severity and the frequency of both CCR6+ SWM and CXCR4+ SWM B cells. Conclusions: CCR6+ SWM B cells were identified as potential producers of IgE to α-gal in CAD patients. Additionally, our findings highlighted non-chemotaxis roles of CCL20/CCR6 and CXCL12/CXCR4 signaling in mediating IgE class switching and cell proliferation of SWM B cells respectively. Results may have important implications for a better understanding and better therapeutic approaches for subjects with IgE sensitization to α-gal.","journal":"Frontiers in Cardiovascular Medicine","year":2022,"id":262843,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"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":334949,"name":"Jeffrey M. Wilson","orcid":"0000-0002-5975-1760","position":1,"is_corresponding":false},{"id":362437,"name":"Loren D. Erickson","orcid":"0000-0001-6762-4625","position":2,"is_corresponding":false},{"id":352052,"name":"Lisa J. Workman","orcid":null,"position":3,"is_corresponding":false},{"id":918772,"name":"Hui Qiao","orcid":"0000-0002-2568-5144","position":4,"is_corresponding":false},{"id":490441,"name":"Yanal Ghosheh","orcid":"0000-0002-3733-2098","position":5,"is_corresponding":false},{"id":866784,"name":"Rishab Gulati","orcid":null,"position":6,"is_corresponding":false},{"id":919243,"name":"Chistopher Durant","orcid":null,"position":7,"is_corresponding":false},{"id":841990,"name":"Jenifer Vallejo","orcid":"0000-0002-4836-8854","position":8,"is_corresponding":false},{"id":324387,"name":"Ryosuke Saigusa","orcid":"0000-0002-1640-6182","position":9,"is_corresponding":false},{"id":334951,"name":"Thomas A.E. Platts‐Mills","orcid":"0000-0002-1263-329X","position":10,"is_corresponding":false},{"id":363872,"name":"Angela M. Taylor","orcid":"0000-0003-4927-4320","position":11,"is_corresponding":false},{"id":324398,"name":"Klaus Ley","orcid":"0000-0001-9339-3672","position":12,"is_corresponding":false},{"id":363873,"name":"Coleen A. McNamara","orcid":"0000-0002-0049-9986","position":13,"is_corresponding":false},{"id":495595,"name":"Tanyaporn Pattarabanjird","orcid":"0000-0003-0994-1491","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:26:25.074177Z","pmid":"35097011","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":[]}