Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells

被引:47
作者
Heesters, Balthasar A. [1 ,2 ]
van Megesen, Kyah [1 ]
Tomris, Ilhan [2 ]
de Vries, Robert P. [2 ]
Magri, Giuliana [3 ]
Spits, Hergen [1 ]
机构
[1] Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Inst Infect & Immun, Dept Expt Immunol, Amsterdam, Netherlands
[2] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Chem Biol & Drug Discovery, Utrecht, Netherlands
[3] Inst Hosp Mar Invest Med, Program Inflammatory & Cardiovasc Disorders, Barcelona, Spain
基金
荷兰研究理事会; 欧洲研究理事会;
关键词
FOLLICULAR DENDRITIC CELLS; FIBROBLASTIC RETICULAR CELLS; MOUSE SPLEEN; ACTIVATION; IMMUNITY; BINDING; MEMORY; LOCALIZATION; GENERATION; EXPRESSION;
D O I
10.1084/jem.20210790
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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 pathogenassociated 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.
引用
收藏
页数:22
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