B cells as promising drug targets for autoimmune diseases

B cells have emerged as central therapeutic targets in autoimmune diseases because they contribute to pathogenesis through autoantibody production, antigen presentation, inflammatory cytokine secretion, and the formation of pathogenic immune niches. Although anti-CD20 antibodies established the clinical value of B-cell depletion, incomplete targeting of tissue-resident B cells, plasmablasts, and long-lived plasma cells limits the depth and durability of treatment responses. Recent advances in CD19-directed chimeric antigen receptor T-cell therapy have demonstrated that profound B-cell depletion can induce sustained, drug-free remission in patients with severe refractory autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathies. Allogeneic CAR-T cells and CD19×CD3 or BCMA×CD3 bispecific T-cell engagers may further expand therapeutic access and enable selective targeting of distinct B-lineage compartments. These findings support a shift from chronic immunosuppression toward immune resetting, while highlighting the need to balance efficacy against infections, hypogammaglobulinemia, and loss of protective immunity. Emerging evidence also suggests that pathogenic B-cell states arise before clinically apparent disease. In individuals at risk of rheumatoid arthritis, activated naive B cells with inflammatory, senescence-like, autoreactive, and antigen-presenting properties may contribute to progression from preclinical autoimmunity to inflammatory arthritis. B-cell-directed drug discovery should therefore pursue two complementary goals: deep immune resetting in severe established disease and selective interception of pathogenic B-cell states before irreversible tissue damage occurs. Improved biomarkers and cell-state-specific targets may ultimately enable both durable treatment and prevention of autoimmune disease.