生发中心
生物
免疫系统
B细胞
流式细胞术
断点群集区域
T细胞受体
B细胞受体
免疫学
T细胞
分子生物学
受体
抗体
遗传学
作者
Shaozhe Cai,Yu Chen,Ziwei Hu,Tianshu Zhou,Yanli Huang,Sheng‐Yan Lin,Rongfen Gao,Jixin Zhong,Lingli Dong
标识
DOI:10.1016/j.jaut.2022.102944
摘要
To investigate the landscape of T-B cell interaction, immune receptor profiles and effects of different types of immune responses in the involved tissues of IgG4-RD.Single cell RNA sequencing, bulk sample RNA sequencing, immune receptor repertoire analysis (both BCR and TCR), multi-color flow cytometry, and in-vitro assays with model cells (e.g. EBV-immortalized B cells from IgG4-RD patient) and histologic methods were applied to investigate the immunopathological features of IgG4-RD from multiple aspects.Ectopic germinal center formation was observed in IgG4-RD patients at advanced disease stage, and a large part of B cells in involved tissue were germinal center B cell-like. Germinal center reaction in IgG4-RD led to the irregularities of both TCR and BCR clones in the involved tissues, and limited clonal overlaps among different samples. Enhanced Th1- and Th2-type responses were observed in involved tissues of IgG4-RD and patients with both increased Th1- and Th2-type response related cell subsets possessed more severe inflammatory indices. Analyses to the origin of IGHG4 transcripts in IgG4-RD indicated that IgG4 could be switched from IgM directly, or from other IgG subclasses. In vitro assays with EBV-immortalized B cells, fibroblasts and epithelial cells revealed the effects of Th1-type and Th2-type responses on germinal center reaction, ectopic expression of MHC-II molecules, and formation of tertiary lymphoid structures.Synergistic effects of Th1- and Th2-type responses were involved in the pathogenesis of IgG4-RD via their influences on both acute inflammatory processes and the chronicity and complexity of IgG4-RD.
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