Identification of an anergic B(ND) cell–derived activated B cell population (B(ND)2) in young-onset type 1 diabetes patients

Recent evidence suggests a role for B cells in the pathogenesis of young-onset type 1 diabetes (T1D), wherein rapid progression occurs. However, little is known regarding the specificity, phenotype, and function of B cells in young-onset T1D. We performed a cross-sectional analysis comparing insulin-reactive to tetanus-reactive B cells in the blood of T1D and controls using mass cytometry. Unsupervised clustering revealed the existence of a highly activated B cell subset we term B(ND)2 that falls within the previously defined anergic B(ND) subset. We found a specific increase in the frequency of insulin-reactive B(ND)2 cells in the blood of young-onset T1D donors, which was further enriched in the pancreatic lymph nodes of T1D donors. The frequency of insulin-binding B(ND)2 cells correlated with anti-insulin autoantibody levels. We demonstrate B(ND)2 cells are pre-plasma cells and can likely act as APCs to T cells. These findings identify an antigen-specific B cell subset that may play a role in the rapid progression of young-onset T1D.