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 BND2 that falls within the previously defined anergic BND subset. We found a specific increase in the frequency of insulin-reactive BND2 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 BND2 cells correlated with anti-insulin autoantibody levels. We demonstrate BND2 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.
Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients
Disclosures: The authors declare no competing interests exist.
- Award Id(s): P30DK116073,R03DK129925,K01OD028759
- Award Id(s): 2018PG-T1D053,G-2108-04793
Zachary C. Stensland, Christopher A. Magera, Hali Broncucia, Brittany D. Gomez, Nasha M. Rios-Guzman, Kristen L. Wells, Catherine A. Nicholas, Marynette Rihanek, Maya J. Hunter, Kevin P. Toole, Peter A. Gottlieb, Mia J. Smith; Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients. J Exp Med 7 August 2023; 220 (8): e20221604. doi: https://doi.org/10.1084/jem.20221604
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