{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:37:01Z","timestamp":1782401821225,"version":"3.54.5"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Myasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort of 20 na\u00efve MG patients positive for anti-acetylcholine receptor (AChR) antibodies and 15 healthy controls was analyzed. Peripheral blood mononuclear cells underwent proteomic profiling, flow cytometry (age-associated B cells (ABCs), plasma cells, T follicular helper cells, and regulatory B cells), and western blot validation of nuclear factor kappa-B (NF-\u03baB)\/cellular reticuloendotheliosis oncogene homolog (c-Rel) expression. Clinical severity was assessed using quantitative MG (QMG) scores. Statistical analyses included differential protein expression, pathway enrichment, and receiver operating characteristic (ROC) curve evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proteomics revealed significant activation of the B cell receptor and NF-\u03baB\/c-Rel signaling pathways in MG patients, validated by upregulated NF-\u03baB\/c-Rel expression (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.01). Flow cytometry demonstrated elevated ABCs (CD19<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup>T-bet<jats:sup>+<\/jats:sup>), plasma cells, and T follicular helper cells, alongside reduced regulatory B cells in MG (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). The proportion of ABCs correlated positively with QMG scores (<jats:italic>r<\/jats:italic>\u202f=\u202f0.5015, <jats:italic>p<\/jats:italic>\u202f=\u202f0.024) but not with AChR antibody titers, suggesting antibody-independent mechanisms. ROC analysis identified moderate diagnostic utility of ABCs for moderate-to-severe MG (QMG scores \u2265 6; area under the curve\u202f=\u202f0.68, 95% confidence intervals: 0.42\u20130.94).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study establishes ABCs and NF-\u03baB\/c-Rel signaling as central contributors to AChR-MG immunopathology. Therefore, ABCs may serve as complementary biomarkers for clinical stratification.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1623066","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:08:34Z","timestamp":1755850114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential 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