{"doi":"10.1093/braincomms/fcad060","title":"B lymphocyte responses in Parkinson’s disease and their possible significance in disease progression","abstract":"Abstract Inflammation contributes to Parkinson’s disease pathogenesis. We hypothesized that B lymphocytes are involved in Parkinson’s disease progression. We measured antibodies to alpha-synuclein and tau in serum from patients with rapid eye movement sleep behaviour disorder (n = 79), early Parkinson’s disease (n = 50) and matched controls (n = 50). Rapid eye movement sleep behaviour disorder cases were stratified by risk of progression to Parkinson’s disease (low risk = 30, high risk = 49). We also measured B-cell activating factor of the tumour necrosis factor receptor family, C-reactive protein and total immunoglobulin G. We found elevated levels of antibodies to alpha-synuclein fibrils in rapid eye movement sleep behaviour disorder patients at high risk of Parkinson’s disease conversion (ANOVA, P < 0.001) and lower S129D peptide-specific antibodies in those at low risk (ANOVA, P < 0.001). An early humoral response to alpha-synuclein is therefore detectable prior to the development of Parkinson’s disease. Peripheral B lymphocyte phenotyping using flow cytometry in early Parkinson’s disease patients and matched controls (n = 41 per group) revealed reduced B cells in Parkinson’s disease, particularly in those at higher risk of developing an early dementia [t(3) = 2.87, P = 0.01]. Patients with a greater proportion of regulatory B cells had better motor scores [F(4,24) = 3.612, P = 0.019], suggesting they have a protective role in Parkinson’s disease. In contrast, B cells isolated from Parkinson’s disease patients at higher risk of dementia had greater cytokine (interleukin 6 and interleukin 10) responses following in vitro stimulation. We assessed peripheral blood lymphocytes in alpha-synuclein transgenic mouse models of Parkinson’s disease: they also had reduced B cells, suggesting this is related to alpha-synuclein pathology. In a toxin-based mouse model of Parkinson’s disease, B-cell deficiency or depletion resulted in worse pathological and behavioural outcomes, supporting the conclusion that B cells play an early protective role in dopaminergic cell loss. In conclusion, we found changes in the B-cell compartment associated with risk of disease progression in rapid eye movement sleep behaviour disorder (higher alpha-synuclein antibodies) and early Parkinson’s disease (lower levels of B lymphocytes that were more reactive to stimulation). Regulatory B cells play a protective role in a mouse model, potentially by attenuating inflammation and dopaminergic cell loss. B cells are therefore likely to be involved in the pathogenesis of Parkinson’s disease, albeit in a complex way, and thus warrant consideration as a therapeutic target.","journal":"Brain Communications","year":2023,"id":321355,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1034002,"name":"Yen Ting Chong","orcid":null,"position":1,"is_corresponding":false},{"id":1033412,"name":"Seoyoung Park","orcid":"0000-0001-7340-2594","position":2,"is_corresponding":false},{"id":283326,"name":"Ruwani Wijeyekoon","orcid":null,"position":3,"is_corresponding":false},{"id":1034003,"name":"Shaista Hayat","orcid":null,"position":4,"is_corresponding":false},{"id":244171,"name":"Rebeccah J. Mathews","orcid":null,"position":5,"is_corresponding":false},{"id":238774,"name":"Zachary Fitzpatrick","orcid":null,"position":6,"is_corresponding":false},{"id":1034004,"name":"Pam Tyers","orcid":null,"position":7,"is_corresponding":false},{"id":1034005,"name":"G. H. VON WRIGHT","orcid":null,"position":8,"is_corresponding":false},{"id":1034006,"name":"Jennifer Whitby","orcid":null,"position":9,"is_corresponding":false},{"id":71645,"name":"Roger A. Barker","orcid":"0000-0001-8843-7730","position":10,"is_corresponding":false},{"id":269035,"name":"Michele T Hu","orcid":null,"position":11,"is_corresponding":false},{"id":250777,"name":"Caroline H. Williams‐Gray","orcid":"0000-0002-2648-9743","position":12,"is_corresponding":false},{"id":15662,"name":"Menna R. Clatworthy","orcid":"0000-0002-3340-9828","position":13,"is_corresponding":false},{"id":235860,"name":"Kirsten M. Scott","orcid":"0000-0003-3121-5963","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"36993946","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":[]}