小柯机器人

瑞士免疫生物学研究所Burkhard Ludewig研究团队近日取得一项新成果。他们发现明区和暗区滤泡树突状细胞的重塑控制生发中心(GC)反应。该研究于2020年5月18日发表在《自然-免疫学》杂志上。

研究人员对表达Cxcl13细胞进行了基因定位以确定B细胞相互作用网状细胞（BRC）组成的分子特征。单细胞转录组学分析表明，在原代B细胞滤泡中BRC亚基的特征是预先确定的。明区和暗区滤泡树突状细胞的进一步拓扑重塑需要CXCL12依赖的与B细胞之间的交互作用，并通过将B细胞保留在滤泡中并控制它们与滤泡辅助性T细胞的相互作用来指示GC输出。

总之，这项研究结果表明，以BRC为基础微环境的稳态可作为指示GC反应效率的前反馈系统。

研究人员表示，GC的有效产生需要B细胞在以特化B细胞相互作用网状细胞为基础的不同微环境之间定向运动。如何对BRC进行重新编程以适应不断发展的GC尚不清楚，并且缺乏对B细胞滤泡内细胞组成的理解极大地阻碍了对该过程的研究。

附：英文原文

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

Author: Natalia B. Pikor, Urs Mrbe, Mechthild Ltge, Cristina Gil-Cruz, Christian Perez-Shibayama, Mario Novkovic, Hung-Wei Cheng, Csar Nombela-Arrieta, Takashi Nagasawa, Michelle A. Linterman, Lucas Onder, Burkhard Ludewig

Issue&Volume: 2020-05-18

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.

DOI: 10.1038/s41590-020-0672-y

Source: https://www.nature.com/articles/s41590-020-0672-y

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
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