{"doi":"10.3389/fimmu.2021.695220","title":"Auto-Antibody Production During Experimental Atherosclerosis in ApoE-/- Mice","abstract":"Current models stipulate that B cells and antibodies function during atherosclerosis in two distinct ways based on antibody isotype, where IgM is protective and IgG is inflammatory. To examine this model, we generated ApoE -/- Aid -/- mice, which are unable to produce IgG antibodies due to the absence of activation-induced deaminase (AID) but maintain high plasma cholesterol due to the absence of apolipoprotein E (APOE). We saw a dramatic decrease in plaque formation in ApoE -/- Aid -/- mice compared to ApoE -/- mice. Rigorous analysis of serum antibodies revealed both ApoE -/- and ApoE -/- Aid -/- mice had substantially elevated titers of IgM antibodies compared to C57BL/6J controls, suggesting a more complex dynamic than previously described. Analysis of antigen specificity demonstrated that ApoE -/- Aid -/- mice had elevated titers of antibodies specific to malondialdehyde-oxidized low density lipoprotein (MDA-oxLDL), which has been shown to block macrophage recruitment into plaques. Conversely, ApoE -/- mice showed low levels of MDA-oxLDL specificity, but had antibodies specific to numerous self-proteins. We provide evidence for a hierarchical order of antibody specificity, where elevated levels of MDA-oxLDL specific IgM antibodies inhibit plaque formation. If the level of MDA-oxLDL specific IgM is insufficient, self-reactive IgM and IgG antibodies are generated against debris within the arterial plaque, resulting in increased inflammation and further plaque expansion.","journal":"Frontiers in Immunology","year":2021,"id":172685,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":229684,"name":"Han-Sol Park","orcid":null,"position":1,"is_corresponding":false},{"id":709569,"name":"Kimberly J. Zanotti","orcid":null,"position":2,"is_corresponding":false},{"id":709044,"name":"Juan A. García Álvarez","orcid":"0000-0003-4233-7958","position":3,"is_corresponding":false},{"id":519042,"name":"Jing Zhang","orcid":"0000-0002-9024-6930","position":4,"is_corresponding":false},{"id":3069,"name":"Li Zhang","orcid":"0000-0002-3617-2627","position":5,"is_corresponding":false},{"id":709045,"name":"Richard Telljohann","orcid":"0000-0001-5619-4463","position":6,"is_corresponding":false},{"id":238211,"name":"Mingyi Wang","orcid":"0000-0001-6412-369X","position":7,"is_corresponding":false},{"id":55700,"name":"Edward G. Lakatta","orcid":"0000-0002-4772-0035","position":8,"is_corresponding":false},{"id":692478,"name":"Patricia J. Gearhart","orcid":"0000-0003-1975-4737","position":9,"is_corresponding":false},{"id":345044,"name":"Robert W. Maul","orcid":"0000-0002-6958-8514","position":10,"is_corresponding":false},{"id":709568,"name":"Mark A. Hutchinson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:46:41.424716Z","pmid":"34305930","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":[]}