2025/03/19 by Catherine A. Nicholas, Fatima Tensun, Spencer A. Evans +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Diabetes and associated disorders #T-cell and B-cell Immunology #Immune Cell Function and Interaction
paper · doi:10.1016/j.celrep.2025.115425
openalex publication_date 2025/03/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Autoreactive B cells play an important but ill-defined role in autoimmune type 1 diabetes (T1D). We isolated pancreatic islet antigen-reactive B cells from the peripheral blood of non-diabetic autoantibody-negative first-degree relatives, autoantibody-positive, and recent-onset T1D donors. Single-cell RNA sequencing analysis revealed that islet antigen-reactive B cells from autoantibody-positive and T1D donors had altered gene expression in pathways associated with B cell signaling and inflammation. Additionally, BCR sequencing uncovered a similar shift in islet antigen-reactive B cell repertoires among autoantibody-positive and T1D donors where greater clonal expansion was also observed. Notably, a substantial fraction of islet antigen-reactive B cells in autoantibody-positive and T1D donors appeared to be polyreactive, which was corroborated by analysis of recombinant monoclonal antibodies. These results expand our understanding of autoreactive B cell phenotypes during T1D and identify unique BCR repertoire changes that may serve as biomarkers for increased disease risk.