Myasthenia thymus reprograms class-switched B cells into BAFF-dependent survivors.

ABSTRACT: Myasthenia gravis (MG) presents a clinical challenge where autoantibody titers against the neuromuscular junction fail to predict disease severity or treatment response, and thymectomy provides inconsistent benefit despite removing the source of autoreactive B cells. We hypothesized that thymic B cells acquire survival mechanisms that bypass normal tolerance checkpoints, enabling persistence independent of antigen-specific selection. Using single-cell RNA sequencing, V(D)J repertoire analysis, and spatial transcriptomics from human thymic samples, representing the largest MG atlas to date (237,661 cells), we discovered a previously unrecognized tolerance checkpoint swap in MG pathogenesis. Pathological class-switched B cells within thymic germinal centers exhibited reduced antigen presenta

SUBMITTER: Yan Y 

PROVIDER: S-EPMC12458123 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature