Institute of Immunity and Transplantation, Division of Infection and Immunity, UCL, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
Department of Pathology and Cell Biology, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA.
Cell Rep. 2020 Nov 17;33(7):108376. doi: 10.1016/j.celrep.2020.108376.
Follicular mature (FM) and germinal center (GC) B cells underpin humoral immunity, but the dynamics of their generation and maintenance are not clearly defined. Here, we exploited a fate-mapping system in mice that tracks B cells as they develop into peripheral subsets, together with a cell division fate reporter mouse and mathematical models. We find that FM cells are kinetically homogeneous, recirculate freely, are continually replenished from transitional populations, and self-renew rarely. In contrast, GC B cell lineages persist for weeks with rapid turnover and site-specific dynamics. Those in the spleen derive from transitional cells and are kinetically homogeneous, while those in lymph nodes derive from FM B cells and comprise both transient and persistent clones. These differences likely derive from the nature of antigen exposure at the different sites. Our integrative approach also reveals how the host environment drives cell-extrinsic, age-related changes in B cell homeostasis.
滤泡成熟 (FM) 和生发中心 (GC) B 细胞是体液免疫的基础，但它们的产生和维持的动态过程尚不清楚。在这里，我们利用一种在小鼠中追踪 B 细胞发育为外周亚群的基因标记系统，结合细胞分裂命运报告小鼠和数学模型进行研究。我们发现 FM 细胞在动力学上是同质的，能够自由循环，不断从过渡群体中得到补充，很少自我更新。相比之下，GC B 细胞谱系能够持续数周，具有快速的更替和特定部位的动态变化。在脾脏中的 GC B 细胞系来源于过渡细胞，在动力学上是同质的，而在淋巴结中的 GC B 细胞系则来源于 FM B 细胞，并包含短暂和持久的克隆。这些差异可能源于不同部位抗原暴露的性质。我们的综合方法还揭示了宿主环境如何驱动 B 细胞稳态的细胞外、与年龄相关的变化。
