{"doi":"10.3389/fimmu.2022.795209","title":"Elevated Detection of Dual Antibody B Cells Identifies Lupus Patients With B Cell-Reactive VH4-34 Autoantibodies","abstract":"About 5% of B cells in healthy mice and humans are allelically or isotypically included and hence co-express two different antibodies. In mice, dual antibody B cells (B 2R ) expand with systemic autoimmunity, co-express autoreactive and non-autoreactive antibodies, and participate in immune responses, but this phenomenon is strain dependent. This study was developed with two goals: 1) to establish the contribution of TLR and IFN receptor signaling to the development of germinal center B cells that express two antibodies in MRL/ lpr mice; and 2) to determine whether B 2R B cells are increased and particularly activated in a subset of adult patients diagnosed with systemic lupus erythematosus (SLE). Results from the MRL/ lpr studies indicate that the enhanced differentiation of dual-κ B cells into germinal center B cells is due to a heightened response to TLR7 and TLR9 signaling, further fueled by an increased response to type II IFN. To understand the clinical and translational implications of our observations in mouse B 2R B cells, cohorts of SLE patients and healthy controls were recruited and evaluated for expression of dual BCRs. Results from flow cytometry and microscopy revealed supraphysiological frequencies of κ + λ + B 2R cells in one fourth of the SLE patients. Abnormal numbers of κ + λ + B cells correlated with higher frequencies of activated naïve B cells and age-associated B cells, and a lower proportion of “B cells that are naïve IgD + ” (BND). However, results from single cell V(D)J sequencing demonstrated that these high κ + λ + SLE patients harbored normal frequencies of κ + λ + and other B 2R B cells. and we further show that their B cells were instead decorated by κ and λ VH4-34 autoantibodies. Thus, our findings indicate that elevated flow cytometric detection of isotypically-included B cells can identify patients with high titers of B cell-reactive VH4-34 autoantibodies and abnormal distribution of B cell subsets relevant to autoimmunity.","journal":"Frontiers in Immunology","year":2022,"id":261751,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":566783,"name":"Susan A. Boackle","orcid":null,"position":1,"is_corresponding":false},{"id":916612,"name":"Sophina H. Taitano","orcid":"0000-0001-9453-4043","position":2,"is_corresponding":false},{"id":917038,"name":"Allison Sang","orcid":null,"position":3,"is_corresponding":false},{"id":489900,"name":"Julie Lang","orcid":"0000-0003-2424-8222","position":4,"is_corresponding":false},{"id":917039,"name":"Margot Kelly","orcid":null,"position":5,"is_corresponding":false},{"id":511684,"name":"Jeremy Rahkola","orcid":null,"position":6,"is_corresponding":false},{"id":364305,"name":"Anjelica M. Miranda","orcid":"0000-0002-8978-2816","position":7,"is_corresponding":false},{"id":225905,"name":"Ryan M. Sheridan","orcid":"0000-0003-4012-3147","position":8,"is_corresponding":false},{"id":263573,"name":"Joshua M. Thurman","orcid":"0000-0002-3476-9956","position":9,"is_corresponding":false},{"id":280640,"name":"V. Koneti Rao","orcid":"0000-0002-7881-6902","position":10,"is_corresponding":false},{"id":351700,"name":"Raul M. Torres","orcid":"0000-0002-5969-5957","position":11,"is_corresponding":false},{"id":489904,"name":"Roberta Pelanda","orcid":"0000-0001-8941-3941","position":12,"is_corresponding":false},{"id":916611,"name":"Jacob N. Peterson","orcid":"0000-0002-3015-9456","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:16.663144Z","pmid":"35185888","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":[]}