Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/120892
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Type: Journal article
Title: B-cell cross-presentation of autologous antigen precipitates diabetes
Author: Mariño, E.
Tan, B.
Binge, L.
Mackay, C.
Grey, S.
Citation: Diabetes, 2012; 61(11):2893-2905
Publisher: American Diabetes Association
Issue Date: 2012
ISSN: 0012-1797
1939-327X
Statement of
Responsibility: 
Eliana Mariño, Bernice Tan, Lauren Binge, Charles R. Mackay and Shane T. Grey
Abstract: For autoimmune conditions like type 1 diabetes to progress, self-reactive CD8⁺ T cells would need to interact with peptide-antigen cross-presented on the surface of antigen-presenting cells in a major histocompatibility complex (MHC) class I-restricted fashion. However, the mechanisms by which autoantigen is cross-presented remain to be identified. In this study, we show cross-presentation of islet-derived autoantigens by B cells. B cells engage self-reactive CD8⁺ T cells in the pancreatic lymph node, driving their proliferative expansion and differentiation into granzyme B⁺interferon-γ⁺lysosomal-associated membrane protein 1⁺ effector cells. B-cell cross-presentation of insulin required proteolytic cleavage and endosomal localization and was sensitive to inhibitors of protein trafficking. Absent B-cell MHC class I, or B-cell receptor restriction to an irrelevant specificity, blunted the expansion of self-reactive CD8⁺ T cells, suggesting B-cell antigen capture and presentation are critical in vivo events for CD8 activation. Indeed, the singular loss of B-cell MHC class I subverted the conversion to clinical diabetes in NOD mice, despite the presence of a pool of activated, and B cell-dependent, interleukin-21-expressing Vβ4⁺CD4⁺ T cells. Thus, B cells govern the transition from clinically silent insulitis to frank diabetes by cross-presenting autoantigen to self-reactive CD8⁺ T cells.
Keywords: Lymph Nodes
Rights: © 2012 by the American Diabetes Association.
RMID: 0030125999
DOI: 10.2337/db12-0006
Appears in Collections:Medicine publications

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