Activated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes
Nicholas CA, Tensun FA, Evans SA, Toole KP, Prendergast JE, Broncucia H, Hesselberth JR, Gottlieb PA, Wells KL, Smith MJ.
Applications: ELISA
Reactive species: Human
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Abstract: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."
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Article snippet:The cardiolipin and
APOH antibodies were gifts from Elena Hsieh who obtained them from Creative Diagnostics."
Figure 1. Antigen-reactive BCR V(D)J sequences were confirmed by ELISA
Publication (1)
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