{"doi":"10.1172/jci182790","title":"Transcriptomic profiling after B cell depletion reveals central and peripheral immune cell changes in multiple sclerosis","abstract":"Multiple sclerosis (MS) is a complex, genetically mediated autoimmune disease of the CNS, in which anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. Although previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic effect on the patient's immune landscape is unknown. In this study, we explored how B cell-depleting therapies modulate the immune landscape using single-cell RNA-Seq. We demonstrate that B cell depletion led to cell-type-specific changes in the abundance and function of cerebrospinal fluid (CSF) macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an antiinflammatory transcriptomic signature and peripheral CD16+ monocytes increased in frequency after B cell depletion. This was accompanied by increases in TNF-α mRNA and protein levels in monocytes following B cell depletion, consistent with the finding that anti-TNF-α treatment exacerbated autoimmune activity in MS. In parallel, B cell depletion induced changes in peripheral CD4+ T cell populations, including increases in the frequency of TIGIT+ Tregs and marked decreases in the frequency of myelin peptide-loaded, tetramer-binding CD4+ T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different cell-type-specific reprogramming as a result of B cell depletion treatment of MS.","journal":"Journal of Clinical Investigation","year":2025,"id":515606,"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":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1327955,"name":"Jeonghyeon Moon","orcid":"0000-0002-5384-4077","position":1,"is_corresponding":false},{"id":1327956,"name":"Yoshiaki Yasumizu","orcid":"0000-0002-9872-4909","position":2,"is_corresponding":false},{"id":69461,"name":"Le Zhang","orcid":"0000-0002-4860-831X","position":3,"is_corresponding":false},{"id":1328416,"name":"Khadir Radassi","orcid":null,"position":4,"is_corresponding":false},{"id":1129327,"name":"Nicholas Buitrago-Pocasangre","orcid":"0000-0002-1333-4435","position":5,"is_corresponding":false},{"id":308941,"name":"M. Elizabeth Deerhake","orcid":"0000-0003-4061-5766","position":6,"is_corresponding":false},{"id":1379939,"name":"Nicolas Strauli","orcid":"0000-0001-8575-006X","position":7,"is_corresponding":false},{"id":643832,"name":"Chun-Wei Chen","orcid":null,"position":8,"is_corresponding":false},{"id":1327957,"name":"Ann Herman","orcid":"0000-0003-3947-0213","position":9,"is_corresponding":false},{"id":987921,"name":"Rosetta Pedotti","orcid":null,"position":10,"is_corresponding":false},{"id":884347,"name":"Catarina Raposo","orcid":"0000-0002-1466-1542","position":11,"is_corresponding":false},{"id":452052,"name":"Isaiah Yim","orcid":null,"position":12,"is_corresponding":false},{"id":261874,"name":"Jenna L. Pappalardo","orcid":"0000-0002-5542-3356","position":13,"is_corresponding":false},{"id":281941,"name":"Erin E. Longbrake","orcid":"0000-0002-1179-3937","position":14,"is_corresponding":false},{"id":49152,"name":"Tomokazu S. Sumida","orcid":"0000-0002-9806-2642","position":15,"is_corresponding":false},{"id":291529,"name":"Pierre‐Paul Axisa","orcid":"0000-0003-1446-3922","position":16,"is_corresponding":false},{"id":37332,"name":"David A. Hafler","orcid":"0000-0003-4664-535X","position":17,"is_corresponding":false},{"id":438162,"name":"Jessica Wei","orcid":"0000-0002-7329-2812","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"40067358","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":[]}