دورية أكاديمية
Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.
| العنوان: | Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes. |
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| المؤلفون: | Thompson, WS, Pekalski, ML, Simons, HZ, Smyth, DJ, Castro-Dopico, X, Guo, H, Guy, C, Dunger, DB, Arif, S, Peakman, M, Wallace, C, Wicker, LS, Todd, JA, Ferreira, RC |
| بيانات النشر: | //dx.doi.org/10.1111/cei.12362 Clin Exp Immunol Oxford University Press (OUP) |
| سنة النشر: | 2014 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | B lymphocytes, IL-2, IL-21, PTPN22, human immunology, immunophenotyping, type 1 diabetes, Adolescent, Adult, Age Factors, Autoantibodies, B-Lymphocyte Subsets, Case-Control Studies, Child, Cytokines, Diabetes Mellitus, Type 1, Female, Flow Cytometry, Gene Expression Regulation, Genetic Association Studies, Humans, Male, Phenotype, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Signal Transduction, Young Adult |
| الوصف: | The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/302561Test |
| DOI: | 10.17863/CAM.49629 |
| الإتاحة: | https://doi.org/10.17863/CAM.49629Test https://www.repository.cam.ac.uk/handle/1810/302561Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.56A62419 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.49629 |
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