{"doi":"10.1016/j.celrep.2020.108330","title":"Complement C4A Regulates Autoreactive B Cells in Murine Lupus","abstract":"Systemic lupus erythematosus (SLE) is a severe autoimmune disease mediated by pathogenic autoantibodies. While complement protein C4 is associated with SLE, its isoforms (C4A and C4B) are not equal in their impact. Despite being 99% homologous, genetic studies identified C4A as more protective than C4B. By generating gene-edited mouse strains expressing either human C4A or C4B and crossing these with the 564lgi lupus strain, we show that, overall, C4A-like 564Igi mice develop less humoral autoimmunity than C4B-like 564Igi mice. This includes a decrease in the number of GCs, autoreactive B cells, autoantibodies, and memory B cells. The higher efficiency of C4A in inducing self-antigen clearance is associated with the follicular exclusion of autoreactive B cells. These results explain how the C4A isoform is protective in lupus and suggest C4A as a possible replacement therapy in lupus.","journal":"Cell Reports","year":2020,"id":101903,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":16706,"name":"Jessy Présumey","orcid":null,"position":1,"is_corresponding":false},{"id":498655,"name":"Cees E. van der Poel","orcid":null,"position":2,"is_corresponding":false},{"id":498104,"name":"Carlos Castrillón","orcid":"0000-0003-2909-7371","position":3,"is_corresponding":false},{"id":498105,"name":"Sarah E. Chang","orcid":"0009-0008-9986-1666","position":4,"is_corresponding":false},{"id":22091,"name":"Paul J. Utz","orcid":"0000-0003-1181-1565","position":5,"is_corresponding":false},{"id":16703,"name":"Michael C. Carroll","orcid":"0000-0002-3213-4295","position":6,"is_corresponding":false},{"id":498654,"name":"Léa Simoni","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T22:40:22.678835Z","pmid":"33147456","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":[]}