Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Barbara Davis Center for Diabetes, University of Colorado School of Medicine , Aurora, CO, USA.
J Exp Med. 2023 Aug 7;220(8). doi: 10.1084/jem.20221604. Epub 2023 May 15.
Recent evidence suggests a role for B cells in the pathogenesis of young-onset type 1 diabetes (T1D), wherein rapid progression occurs. However, little is known regarding the specificity, phenotype, and function of B cells in young-onset T1D. We performed a cross-sectional analysis comparing insulin-reactive to tetanus-reactive B cells in the blood of T1D and controls using mass cytometry. Unsupervised clustering revealed the existence of a highly activated B cell subset we term BND2 that falls within the previously defined anergic BND subset. We found a specific increase in the frequency of insulin-reactive BND2 cells in the blood of young-onset T1D donors, which was further enriched in the pancreatic lymph nodes of T1D donors. The frequency of insulin-binding BND2 cells correlated with anti-insulin autoantibody levels. We demonstrate BND2 cells are pre-plasma cells and can likely act as APCs to T cells. These findings identify an antigen-specific B cell subset that may play a role in the rapid progression of young-onset T1D.
最近的证据表明 B 细胞在年轻起病的 1 型糖尿病（T1D）的发病机制中起作用，其中疾病进展迅速。然而，对于年轻起病的 T1D 患者血液中的 B 细胞的特异性、表型和功能知之甚少。我们使用质谱流式细胞术对 T1D 和对照组患者血液中的胰岛素反应性 B 细胞与破伤风反应性 B 细胞进行了横断面分析。无监督聚类显示存在一个高度激活的 B 细胞亚群，我们称之为 BND2，它属于先前定义的无反应性 BND 亚群。我们发现年轻起病的 T1D 供体血液中胰岛素反应性 BND2 细胞的频率特异性增加，而 T1D 供体的胰腺淋巴结中这种细胞进一步富集。胰岛素结合的 BND2 细胞的频率与抗胰岛素自身抗体水平相关。我们证明 BND2 细胞是前浆细胞，可能作为 APC 作用于 T 细胞。这些发现确定了一个可能在年轻起病的 T1D 快速进展中起作用的抗原特异性 B 细胞亚群。
