biostudies-literatureStensland ZCNetwork for Pancreatic Organ DonorsLeona M. and Harry B. Helmsley Charitable TrustNIDDK NIH HHSNational Institutes of HealthJDRFNIH HHSe20221604https://www.ebi.ac.uk/biostudies/studies/S-EPMC10192302biostudies-literatureUnknown220(8)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 aThe Journal of experimental medicineIdentification of an anergic BND cell-derived activated B cell population (BND2) in young-onset type 1 diabetes patients.PMC10192302P30DK116073K01OD028759P30 DK116073R03 DK129925R03DK129925R03 OD036470G-2108-047932018PG-T1D053K01 OD028759Stensland ZCWells KLSmith MJRihanek MRios-Guzman NMGottlieb PAGomez BDNicholas CAHunter MJMagera CAToole KPBroncucia HfalseIdentification 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 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 a2023-01-01T00:00:00Z2023 Aug2026-04-29T02:24:05.795Z2024-11-07T02:43:21.178ZS-EPMC101923023718456310.1084/jem.20221604