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Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Myasthenia gravis (MG) presents a clinical challenge where autoantibody titers poorly predict disease severity, and thymectomy provides inconsistent benefits. We hypothesized that thymic B cells acquire survival mechanisms that bypass canonical tolerance checkpoints, enabling persistence independent of antigen-specific selection. Using single-cell RNA sequencing, V(D)J repertoire analysis, and spatial transcriptomics to generate the largest MG atlas to date (237,661 cells), we identified a tolerance checkpoint swap in MG pathogenesis. Pathological class-switched B cells within thymic germinal centers exhibited reduced antigen presentation (\n                    <jats:italic toggle=\"yes\">CD74<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">CD1C<\/jats:italic>\n                    ) and diminished\n                    <jats:italic toggle=\"yes\">CD40<\/jats:italic>\n                    costimulation while up-regulating\n                    <jats:italic toggle=\"yes\">TNFRSF17<\/jats:italic>\n                    to engage BAFF-driven survival. This shift allows polyclonal autoreactive B cells to evade stringent selection and seed peripheral sites. T follicular helper cells supported this reprogramming via increased\n                    <jats:italic toggle=\"yes\">TNFSF13B<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">CHGB<\/jats:italic>\n                    expression, with the latter facilitating dopamine-mediated synaptic acceleration. These findings offer insight into clinical paradoxes in MG and point to the BAFF-BCMA axis as a potential therapeutic target and biomarkers for disease activity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec3842","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:01:07Z","timestamp":1786557667000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Myasthenia thymus reprograms class-switched B cells into BAFF-dependent survivors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0094-7726","authenticated-orcid":true,"given":"Yuanqing","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Avella","family":"Patino","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Coral Gables, FL 33124, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8878-1098","authenticated-orcid":true,"given":"Yimeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-6344","authenticated-orcid":true,"given":"Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3114-5208","authenticated-orcid":true,"given":"G. R. Scott","family":"Budinger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1248-0457","authenticated-orcid":true,"given":"Ankit","family":"Bharat","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, 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