Permissive central tolerance plus defective peripheral checkpoints license pathogenic memory B cells in CASPR2-antibody encephalitis

In this cutting-edge study, Bo Sun et al. demonstrated that both healthy individuals and patients with CASPR2-autoantibody encephalitis can possess naive CASPR2+ B cells. However, only those with encephalitis develop CASPR2-reactive memory B cells, whose BCRs exhibit pathogenic activity both in vitro and in vivo. This suggests that a breakdown of peripheral tolerance to CASPR2 may contribute to the development of CASPR2 encephalitis.