Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/120892
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | B-cell cross-presentation of autologous antigen precipitates diabetes |
Author: | Mariño, E. Tan, B. Binge, L. Mackay, C.R. Grey, S.T. |
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. |
DOI: | 10.2337/db12-0006 |
Published version: | http://dx.doi.org/10.2337/db12-0006 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.