Identification of an anergic BND cell-derived activated B cell population (BND2) 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. The role of B cells in T1D remains poorly understood. We identified an activated B cell subset that is enriched in insulin reactivity and increased in the blood and pLN of T1D donors. This subset has capacity to secrete antibodies and potential to serve as APCs to T cells.

Automated summary

Recent evidence suggests that a specific subset of B cells, termed B(ND)2, may play a role in the rapid progression of young-onset type 1 diabetes (T1D). These B(ND)2 cells are highly activated and show increased insulin reactivity, correlating with anti-insulin autoantibody levels. They have the capacity to secrete antibodies and serve as antigen-presenting cells (APCs) to T cells. Identifying and understanding the role of these B(ND)2 cells may contribute to the knowledge of T1D pathogenesis.