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Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2021-08-23 , DOI: 10.1084/jem.20210790
Balthasar A Heesters 1 , Kyah van Megesen 1 , Ilhan Tomris 2 , Robert P de Vries 2 , Giuliana Magri 3 , Hergen Spits 1
Affiliation  

Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined. Using single-cell RNA sequencing and microarray, we provided the transcriptome of these enigmatic cells as a comprehensive resource. Key genes were validated by flow cytometry and microscopy. Surprisingly, marginal reticular cells (MRCs) rather than FDCs expressed B cell activating factor (BAFF). Furthermore, we found that human FDCs expressed TLR4 and can alter antigen availability in response to pathogen-associated molecular patterns (PAMPs). High expression of PD-L1 and PD-L2 on FDCs activated PD1 on T cells. In addition, we found expression of genes related to T cell regulation, such as HLA-DRA, CD40, and others. These data suggest intimate contact between human FDCs and T cells.

中文翻译:

人类 FDC 的表征揭示了 T 细胞的调节和向 B 细胞的抗原呈递

基质衍生的滤泡树突细胞 (FDC) 是生发中心 (GC) 必不可少的,而生发中心是 B 细胞使其抗体成熟的部位。FDC 将天然抗原呈递给 B 细胞并保持 CXCL13 梯度以形成 B 细胞滤泡。然而,尽管它们具有重要作用,但人类 FDC 的转录组仍未定义。使用单细胞 RNA 测序和微阵列,我们提供了这些神秘细胞的转录组作为综合资源。通过流式细胞术和显微镜验证关键基因。令人惊讶的是,边缘网状细胞 (MRC) 而非 FDC 表达 B 细胞激活因子 (BAFF)。此外,我们发现人类 FDC 表达 TLR4,并且可以响应病原体相关分子模式 (PAMP) 改变抗原可用性。FDC 上 PD-L1 和 PD-L2 的高表达激活了 T 细胞上的 PD1。此外,HLA-DRACD40等。这些数据表明人类 FDC 和 T 细胞之间的密切接触。
更新日期:2021-08-24
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