被激活的多活性B细胞在自身抗体阳性和最近出现1型糖尿病的患者中被克隆扩张
Catherine A Nicholas1, Fatima A Tensun2, Spencer A Evans2
1Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Molecular Biology Graduate Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cell reports
|March 21, 2025
概括
1型糖尿病 (T1D) 中的自主反应性B细胞显示了基因表达和B细胞受体谱的改变. 这些B细胞的变化可能表明患T1D的风险增加.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 遗传学 遗传学 是一个
背景情况:
- 自主反应性B细胞与1型糖尿病 (T1D) 病原发生有关.
- 它们在T1D中的确切作用和特征仍然不完全理解.
研究的目的:
- 描述具有不同T1D风险的个体中小岛抗原反应性B细胞的表型和B细胞受体 (BCR) 谱.
- 为了确定T1D发展的潜在生物标志物.
主要方法:
- 从整个T1D频谱的捐赠者的外周血液中分离胰岛素抗原反应B细胞.
- 单细胞RNA测序 (scRNA-seq) 用于分析基因表达.
- 测序BCR测序以评估曲目多样性和克隆扩张.
- 对重组单克隆抗体的分析以确认多活性.
主要成果:
- 来自自身抗体阳性和T1D捐赠者的岛屿抗原反应性B细胞在B细胞信号和炎症通路中表现出改变的基因表达.
- BCR测序揭示了小岛抗原反应性B细胞目录的融合转变以及自身抗体阳性和T1D捐赠者的克隆扩张的增加.
- 很大一部分B细胞表现出多活性,抗体分析证实了这一点.
结论:
- 改变基因表达和BCR谱系动态的特征是T1D和高风险个体的自身反应性B细胞.
- 这些发现提高了对T1D自身免疫的理解,并表明了疾病风险分层的潜在基于BCR的生物标志物.
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