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明暗区滤泡树突状细胞的重塑调控生发中心反应。

Remodeling of light and dark zone follicular dendritic cells governs germinal center responses.

作者信息

Pikor Natalia B, Mörbe Urs, Lütge Mechthild, Gil-Cruz Cristina, Perez-Shibayama Christian, Novkovic Mario, Cheng Hung-Wei, Nombela-Arrieta César, Nagasawa Takashi, Linterman Michelle A, Onder Lucas, Ludewig Burkhard

机构信息

Institute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Department of Experimental Hematology and Oncology, University Hospital and University of Zurich, Zurich, Switzerland.

出版信息

Nat Immunol. 2020 Jun;21(6):649-659. doi: 10.1038/s41590-020-0672-y. Epub 2020 May 18.

DOI:10.1038/s41590-020-0672-y
PMID:32424359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7610477/
Abstract

Efficient generation of germinal center (GC) responses requires directed movement of B cells between distinct microenvironments underpinned by specialized B cell-interacting reticular cells (BRCs). How BRCs are reprogrammed to cater to the developing GC remains unclear, and studying this process is largely hindered by incomplete resolution of the cellular composition of the B cell follicle. Here we used genetic targeting of Cxcl13-expressing cells to define the molecular identity of the BRC landscape. Single-cell transcriptomic analysis revealed that BRC subset specification was predetermined in the primary B cell follicle. Further topological remodeling of light and dark zone follicular dendritic cells required CXCL12-dependent crosstalk with B cells and dictated GC output by retaining B cells in the follicle and steering their interaction with follicular helper T cells. Together, our results reveal that poised BRC-defined microenvironments establish a feed-forward system that determines the efficacy of the GC reaction.

摘要

生发中心（GC）反应的高效产生需要B细胞在由专门的B细胞相互作用网状细胞（BRC）支持的不同微环境之间定向移动。BRC如何被重新编程以适应发育中的GC仍不清楚，而研究这一过程在很大程度上受到B细胞滤泡细胞组成解析不完整的阻碍。在这里，我们使用对表达Cxcl13的细胞进行基因靶向来定义BRC景观的分子特征。单细胞转录组分析表明，BRC亚群的特化在初级B细胞滤泡中是预先确定的。明暗区滤泡树突状细胞的进一步拓扑重塑需要与B细胞进行依赖CXCL12的串扰，并通过将B细胞保留在滤泡中并引导它们与滤泡辅助性T细胞的相互作用来决定GC输出。总之，我们的结果表明，由BRC定义的平衡微环境建立了一个前馈系统，该系统决定了GC反应的效力。

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