Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/120892
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DC Field | Value | Language |
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dc.contributor.author | Mariño, E. | - |
dc.contributor.author | Tan, B. | - |
dc.contributor.author | Binge, L. | - |
dc.contributor.author | Mackay, C.R. | - |
dc.contributor.author | Grey, S.T. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Diabetes, 2012; 61(11):2893-2905 | - |
dc.identifier.issn | 0012-1797 | - |
dc.identifier.issn | 1939-327X | - |
dc.identifier.uri | http://hdl.handle.net/2440/120892 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Eliana Mariño, Bernice Tan, Lauren Binge, Charles R. Mackay and Shane T. Grey | - |
dc.language.iso | en | - |
dc.publisher | American Diabetes Association | - |
dc.rights | © 2012 by the American Diabetes Association. | - |
dc.source.uri | http://dx.doi.org/10.2337/db12-0006 | - |
dc.subject | Lymph Nodes | - |
dc.title | B-cell cross-presentation of autologous antigen precipitates diabetes | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.2337/db12-0006 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Grey, S.T. [0000-0003-2160-1625] | - |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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