{"title":"The Role of B Lymphocytes in Type 1 Diabetes","authors":"Mia J. Smith, Joanne Boldison, F. Susan Wong","doi":"10.1101/cshperspect.a041593","DOIUrl":null,"url":null,"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.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"195 1","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor perspectives in medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1101/cshperspect.a041593","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
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.
众所周知,自身反应性 T 细胞会诱导 1 型糖尿病(T1D)β 细胞死亡,而自身反应性 B 细胞在 T1D 的发病机制中也扮演着重要角色。研究表明,T1D 患者体内自我反应性 B 细胞的出现频率增加,这些 B 细胞从骨髓中逃逸出来,在外周器官中增殖、活化并参与疾病的发生。这些失效的耐受机制可能与 T1D 发病相关的遗传风险等位基因有关。一旦进入外周,这些自我反应性 B 细胞就会成为自反应性 T 细胞的重要抗原递呈细胞,并产生自身抗体,用于预测有 T1D 风险或被诊断为 T1D 的个体。在这里,我们将讨论 B 细胞在 T1D 发病机制中起重要作用的证据、这些细胞如何逃避正常的耐受机制、它们在疾病进展中的作用,以及靶向这些细胞和/或监测它们作为治疗反应的生物标志物将如何对临床有益。
期刊介绍:
Cold Spring Harbor Perspectives in Medicine is a monthly online publication comprising reviews on different aspects of a variety of diseases, covering everything from the molecular and cellular bases of disease to translational medicine and new therapeutic strategies.
Cold Spring Harbor Perspectives in Medicine is thus unmatched in its depth of coverage and represents an essential source where readers can find informed surveys and critical discussion of advances in molecular medicine.