Identification of an anergic BND cell-derived activated B cell population (BND2) in young-onset type 1 diabetes patients.
Identification of an anergic BND cell-derived activated B cell population (BND2) in young-onset type 1 diabetes patients.
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DOI：
10.1084/jem.20221604
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发表时间：
2023-08-07
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--
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B细胞在T1D中的作用仍然知之甚少。我们鉴定了一种活化的B细胞亚群，其富含胰岛素反应性，并且在T1D供体的血液和pLN中增加。该亚群具有分泌抗体的能力和充当T细胞的APC的潜力。最近的证据表明B细胞在快速进展的1型糖尿病（T1D）发病机制中的作用。然而，关于B细胞的特异性、表型和功能在T1型糖尿病中的作用知之甚少。我们进行了一项横断面分析，比较了T1D患者和对照组血液中胰岛素反应性和破伤风反应性B细胞，并使用质谱细胞术。无监督聚类显示存在高度活化的B细胞亚群，我们称之为BND 2，其福尔斯落入先前定义的无反应性BND亚群内。我们发现胰岛素反应性BND 2细胞在初发T1D供体血液中的频率特异性增加，其在T1D供体的胰腺淋巴结中进一步富集。胰岛素结合BND2细胞的频率与抗胰岛素自身抗体水平相关。我们证明BND 2细胞是前浆细胞，并且可能充当T细胞的APC。这些发现确定了一个抗原特异性B细胞亚群，可能在快速进展的T1D中发挥作用。
The role of B cells in T1D remains poorly understood. We identified an activated B cell subset that is enriched in insulin reactivity and increased in the blood and pLN of T1D donors. This subset has capacity to secrete antibodies and potential to serve as APCs to T cells. 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.
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