List of antibodies used.

Persistent germinal center (GC) responses show increased benefit in optimal responses to influenza infection. Follicular helper T (TFH) cells provide the essential signals and help for maintenance of GCs and require IL-1β signaling for establishment and maintenance. We observe a preferential upregulation of IL-1β within GC B cells and coexpression of NLRP3 and caspase-1 with IL-1β confirms that GC B cells process IL-1β using a canonical NLRP3/caspase-1 mechanism. Using B cell specific ablation of IL-1β production and IL-1β signaling we further confirm that, GC B cells are the primary source of vital IL-1β within the GC and that IL-1β processing by GC B cells post influenza infection is driven by NLRP3 inflammasomes. We observe significant reduction of GC B cells and TFH cells in the absence of B cell derived IL-1β and our analysis of human B cells suggests similar mechanisms in human GC B cells. Our data present GC B cells in two novel roles, the first in producing IL-1β, which is associated with innate functions, within the GC and the second is providing helper cytokine to the TFH cell. Our findings add to the known complexity of the GC providing a target to enhance GC function and persistence.

持续性生发中心（germinal center, GC）应答在机体针对流感病毒感染的最优应答中可发挥更显著的保护效应。滤泡辅助性T（follicular helper T, TFH）细胞可为生发中心的维持提供必需信号与辅助支持，其自身的建立与维持亦依赖白细胞介素1β（IL-1β）信号通路。本研究观察到，IL-1β在GC B细胞内呈现优先上调表达；而NLRP3与半胱天冬氨酸蛋白酶1（caspase-1）和IL-1β的共表达现象证实，GC B细胞通过经典的NLRP3/caspase-1通路加工产生IL-1β。通过特异性敲除B细胞的IL-1β产生能力与IL-1β信号通路，本研究进一步证实：GC B细胞是生发中心内关键性IL-1β的主要来源，且流感病毒感染后，GC B细胞对IL-1β的加工过程由NLRP3炎性体驱动。研究发现，在B细胞来源的IL-1β缺失条件下，GC B细胞与TFH细胞的数量显著减少；而针对人类B细胞的分析表明，人类GC B细胞中存在类似的调控机制。本研究揭示了GC B细胞的两种全新功能：其一为在生发中心微环境中产生具有先天免疫功能的IL-1β，其二为向TFH细胞提供辅助性细胞因子。本研究结果进一步丰富了人们对生发中心应答复杂性的认知，并为增强GC功能与持久性提供了潜在干预靶点。