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.
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May 15 2023
Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients
In Special Collection:
B cells, Infectious Diseases, and Autoimmunity
Zachary C. Stensland
,
Zachary C. Stensland
(Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Christopher A. Magera
,
Christopher A. Magera
(Data curation, Investigation)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Hali Broncucia
,
Hali Broncucia
(Investigation, Supervision)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Brittany D. Gomez
,
Brittany D. Gomez
(Formal analysis, Investigation)
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
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Nasha M. Rios-Guzman
,
Nasha M. Rios-Guzman
(Formal analysis, Investigation)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
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Kristen L. Wells
,
Kristen L. Wells
(Formal analysis, Software, Visualization)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Catherine A. Nicholas
,
Catherine A. Nicholas
(Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
4Department of Biochemistry and Molecular Genetics,
University of Colorado School of Medicine
, Aurora, CO, USA
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Marynette Rihanek,
Marynette Rihanek
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Maya J. Hunter
,
Maya J. Hunter
(Data curation)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Kevin P. Toole
,
Kevin P. Toole
(Data curation, Formal analysis, Investigation, Writing - review & editing)
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Peter A. Gottlieb
,
Peter A. Gottlieb
(Conceptualization, Investigation, Resources, Validation, Writing - review & editing)
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
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Mia J. Smith
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
Correspondence to Mia J. Smith: mia.smith@cuanschutz.edu
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Zachary C. Stensland
Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Christopher A. Magera
Data curation, Investigation
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Hali Broncucia
Investigation, Supervision
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Brittany D. Gomez
Formal analysis, Investigation
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
Nasha M. Rios-Guzman
Formal analysis, Investigation
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
Kristen L. Wells
Formal analysis, Software, Visualization
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Catherine A. Nicholas
Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
4Department of Biochemistry and Molecular Genetics,
University of Colorado School of Medicine
, Aurora, CO, USA
Marynette Rihanek
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Maya J. Hunter
Data curation
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Kevin P. Toole
Data curation, Formal analysis, Investigation, Writing - review & editing
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Peter A. Gottlieb
Conceptualization, Investigation, Resources, Validation, Writing - review & editing
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
Mia J. Smith
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Pediatrics,
University of Colorado School of Medicine
, Aurora, CO, USA
2
Barbara Davis Center for Diabetes, University of Colorado School of Medicine
, Aurora, CO, USA
3Department of Immunology and Microbiology,
University of Colorado School of Medicine
, Aurora, CO, USA
Correspondence to Mia J. Smith: mia.smith@cuanschutz.edu
Disclosures: The authors declare no competing interests exist.
Received:
September 15 2022
Revision Received:
March 15 2023
Accepted:
April 21 2023
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
National Institutes of Health
- Award Id(s): P30DK116073,R03DK129925,K01OD02875
Funder(s):
JDRF
Funder(s):
Leona M. and Harry B. Helmsley Charitable Trust
- Award Id(s): 2018PG-T1D053,G-2108-04793
Funder(s):
Network for Pancreatic Organ Donors
© 2023 Stensland et al.
2023
Stensland et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2023) 220 (8): e20221604.
Article history
Received:
September 15 2022
Revision Received:
March 15 2023
Accepted:
April 21 2023
Citation
Zachary C. Stensland, Christopher A. Magera, Hali Broncucia, Brittany D. Gomez, Nasha M. Rios-Guzman, Kristen L. Wells, Catherine A. Nicholas, Marynette Rihanek, Maya J. Hunter, Kevin P. Toole, Peter A. Gottlieb, Mia J. Smith; Identification of an anergic BND cell–derived activated B cell population (BND2) in young-onset type 1 diabetes patients. J Exp Med 7 August 2023; 220 (8): e20221604. doi: https://doi.org/10.1084/jem.20221604
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