دورية أكاديمية
Interleukin-10+ regulatory b cells arise within antigen-experienced CD40+ B cells to maintain tolerance to islet autoantigens
| العنوان: | Interleukin-10+ regulatory b cells arise within antigen-experienced CD40+ B cells to maintain tolerance to islet autoantigens |
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| المؤلفون: | S. Kleffel, A. Vergani, S. Tezza, M. B. Nasr, M. A. Niewczas, S. Wong, R. Bassi, F. D'Addio, T. Schatton, R. Abdi, M. Atkinson, M. H. Sayegh, L. Wen, C. H. Wasserfall, K. C. O'Connor, P. Fiorina, M. Ben Nasr |
| المساهمون: | S. Kleffel, A. Vergani, S. Tezza, M.B. Nasr, M.A. Niewcza, S. Wong, R. Bassi, F. D'Addio, T. Schatton, R. Abdi, M. Atkinson, M.H. Sayegh, L. Wen, C.H. Wasserfall, K.C. O'Connor, P. Fiorina, M. Ben Nasr |
| بيانات النشر: | American Diabetes Association |
| سنة النشر: | 2015 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Adult, Animal, Antigens, CD40, Autoantigen, B-Lymphocytes, Regulatory, Diabetes Mellitus, Type 1, Female, Human, Immune Tolerance, Interleukin-10, Islets of Langerhan, Male, Mice, Inbred C57BL, Inbred NOD, SCID, Transgenic, Middle Aged, Transcriptome, Young Adult, Internal Medicine, Endocrinology, Diabetes and Metabolism, Medicine (all), Settore MED/13 - Endocrinologia |
| الوصف: | Impaired regulatory B cell (Breg) responses are associated with several autoimmune diseases in humans; however, the role of Bregs in type 1 diabetes (T1D) remains unclear. We hypothesized that naturally occurring, interleukin-10 (IL-10)-producing Bregs maintain tolerance to islet autoantigens, and that hyperglycemic nonobese diabetic (NOD) mice and T1D patients lack these potent negative regulators. IgVH transcriptome analysis revealed that islet-infiltrating B cells in longterm normoglycemic (Lnglc) NOD, which are naturally protected from diabetes, are more antigen-experienced and possess more diverse B-cell receptor repertoires compared to those of hyperglycemic (Hglc) mice. Importantly, increased levels of Breg-promoting CD40+ B cells and IL-10-producing B cells were found within islets of Lnglc compared to Hglc NOD. Likewise, healthy individuals showed increased frequencies of both CD40+ and IL-10+ B cells compared to T1D patients. Rituximabmediated B-cell depletion followed by adoptive transfer of B cells from Hglc mice induced hyperglycemia in Lnglc human CD20 transgenic NOD mouse models. Importantly, both murine and human IL-10+ B cells significantly abrogated T-cell-mediated responses to self- or isletspecific peptides ex vivo. Together, our data suggest that antigen-matured Bregs may maintain tolerance to islet autoantigens by selectively suppressing autoreactive T-cell responses, and that Hglc mice and individuals with T1D lack this population of Bregs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/25187361; info:eu-repo/semantics/altIdentifier/wos/WOS:000346765600017; volume:64; issue:1; firstpage:158; lastpage:171; numberofpages:14; journal:DIABETES; http://hdl.handle.net/2434/484117Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84920059445 |
| DOI: | 10.2337/db13-1639 |
| الإتاحة: | https://doi.org/10.2337/db13-1639Test http://hdl.handle.net/2434/484117Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B78CF529 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db13-1639 |
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