Myasthenia thymus reprograms class switched B cells into BAFF dependent survivors

In Myasthenia gravis (MG), autoantibody titers and thymectomy outcomes often fail to predict disease severity, suggesting that autoreactive B cells bypass normal tolerance checkpoints. Our analysis of the largest MG thymus atlas to date reveals a checkpoint swap where pathological B cells transition from T cell-dependent selection to a BAFF-driven survival program. These B cells exhibit reduced antigen presentation and CD40 co-stimulation, instead upregulating TNFRSF17 to engage BAFF signals provided by specialized T follicular helper cells. This reprogramming allows polyclonal autoreactive populations to persist and seed peripheral sites independent of stringent selection, explaining longstanding clinical paradoxes. Consequently, the BAFF-BCMA axis emerges as a critical therapeutic target and a high-fidelity biomarker for monitoring MG disease activity.