Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients

Author:

Stensland Zachary C.12ORCID,Magera Christopher A.2ORCID,Broncucia Hali2ORCID,Gomez Brittany D.3ORCID,Rios-Guzman Nasha M.23ORCID,Wells Kristen L.2ORCID,Nicholas Catherine A.24ORCID,Rihanek Marynette2,Hunter Maya J.2ORCID,Toole Kevin P.2ORCID,Gottlieb Peter A.12ORCID,Smith Mia J.123ORCID

Affiliation:

1. University of Colorado School of Medicine 1 Department of Pediatrics, , Aurora, CO, USA

2. Barbara Davis Center for Diabetes, University of Colorado School of Medicine 2 , Aurora, CO, USA

3. University of Colorado School of Medicine 3 Department of Immunology and Microbiology, , Aurora, CO, USA

4. University of Colorado School of Medicine 4 Department of Biochemistry and Molecular Genetics, , Aurora, CO, USA

Abstract

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.

Funder

National Institutes of Health

JDRF

Leona M. and Harry B. Helmsley Charitable Trust

Network for Pancreatic Organ Donors

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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