biostudies-literatureUnknownNicholas CANIDDK NIH HHSNIA NIH HHSNCI NIH HHSNIH HHSNIGMS NIH HHSAutoreactive B cells play an important but ill-defined role in autoimmune type 1 diabetes (T1D). To better understand their contribution, we performed single cell gene and BCR-seq analysis on pancreatic islet antigen-reactive (IAR) B cells from the peripheral blood of nondiabetic (ND), autoantibody positive prediabetic (AAB), and recent-onset T1D individuals. We found that the frequency of IAR B cells was increased in AAB and T1D. IAR B cells from these donors had altered expression of B cell signaling, pro-inflammatory, infection, and antigen processing and presentation genes. Both AAB and T1D donors demonstrated a significant increase in certain heavy and light chain V genes, and these V genes were enriched in islet-reactivity. Public clones of IAR B cells were restricted almost entirelybioRxiv : the preprint server for biology2024.06.20.599914https://www.ebi.ac.uk/biostudies/studies/S-EPMC11230262biostudies-literatureIslet-antigen reactive B cells display a unique phenotype and BCR repertoire in autoantibody positive and recent-onset type 1 diabetes patients.PMC11230262P30 CA046934P30 DK116073F31 DK134095T32 GM136444R01 AG071467K01 OD028759Evans SAWells KLSmith MJTensun FAGottlieb PANicholas CAToole KPBroncucia HHesselberth JRfalseIslet-antigen reactive B cells display a unique phenotype and BCR repertoire in autoantibody positive and recent-onset type 1 diabetes patients.Autoreactive B cells play an important but ill-defined role in autoimmune type 1 diabetes (T1D). To better understand their contribution, we performed single cell gene and BCR-seq analysis on pancreatic islet antigen-reactive (IAR) B cells from the peripheral blood of nondiabetic (ND), autoantibody positive prediabetic (AAB), and recent-onset T1D individuals. We found that the frequency of IAR B cells was increased in AAB and T1D. IAR B cells from these donors had altered expression of B cell signaling, pro-inflammatory, infection, and antigen processing and presentation genes. Both AAB and T1D donors demonstrated a significant increase in certain heavy and light chain V genes, and these V genes were enriched in islet-reactivity. Public clones of IAR B cells were restricted almost entirely2024-01-01T00:00:00Z2024 Jun2026-06-30T03:17:36.821Z2025-04-04T01:54:34.902ZS-EPMC112302623897937610.1101/2024.06.20.599914