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B淋巴细胞在1型糖尿病中的作用。

The Role of B Lymphocytes in Type 1 Diabetes.

作者信息

Smith Mia J, Boldison Joanne, Wong F Susan

机构信息

Department of Pediatrics, Barbara Davis Center for Diabetes, The University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA

Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter EX2 5DW, United Kingdom

出版信息

Cold Spring Harb Perspect Med. 2024 Aug 12. doi: 10.1101/cshperspect.a041593.

Abstract

While autoreactive T cells are known to induce β-cell death in type 1 diabetes (T1D), self-reactive B cells also play an important role in the pathogenesis of T1D. Studies have shown that individuals living with T1D have an increased frequency of self-reactive B cells that escape from the bone marrow and populate peripheral organs, become activated, and participate in disease. These failed tolerance mechanisms may be attributed to genetic risk alleles that are associated with the development of T1D. Once in the periphery, these self-reactive B cells act as important antigen-presenting cells to autoreactive T cells and produce autoantibodies that are used to predict individuals at risk for or diagnosed with T1D. Here, we discuss the evidence that B cells are important in the pathogenesis of T1D, how these cells escape normal tolerance mechanisms, their role in disease progression, and how targeting these cells and/or monitoring them as biomarkers for response to therapy will be of clinical benefit.

摘要

虽然已知自身反应性T细胞会在1型糖尿病(T1D)中诱导β细胞死亡,但自身反应性B细胞在T1D的发病机制中也起着重要作用。研究表明,患有T1D的个体中,从骨髓逃逸并在外周器官中聚集、被激活并参与疾病的自身反应性B细胞频率增加。这些失败的耐受机制可能归因于与T1D发展相关的遗传风险等位基因。一旦进入外周,这些自身反应性B细胞就会作为重要的抗原呈递细胞作用于自身反应性T细胞,并产生用于预测有T1D风险或已被诊断为T1D的个体的自身抗体。在此,我们讨论B细胞在T1D发病机制中重要性的证据、这些细胞如何逃避正常耐受机制、它们在疾病进展中的作用,以及将这些细胞作为治疗反应的生物标志物进行靶向和/或监测如何具有临床益处。

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