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.

中文翻译：

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亮区和暗区滤泡树突状细胞的重塑控制生发中心反应。

要有效地生成生发中心（GC）响应，就需要B细胞在专门的B细胞相互作用网状细胞（BRC）支持的不同微环境之间定向运动。如何对BRCs进行重新编程以适应不断发展的GC尚不清楚，并且对B细胞滤泡的细胞组成的不完全解析极大地阻碍了对该过程的研究。在这里，我们使用Cxcl13表达细胞的遗传靶向来定义BRC景观的分子身份。单细胞转录组学分析表明，在原代B细胞卵泡中BRC亚组的规格是预先确定的。亮区和暗区滤泡树突状细胞的进一步拓扑重塑需要CXCL12依赖于B细胞的串扰，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细胞的相互作用来决定GC的输出。总之，我们的结果表明，平衡的BRC定义的微环境建立了确定GC反应效率的前馈系统。