Immunology Program, Babraham Institute, Cambridge, UK.
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Nat Immunol. 2023 Jul;24(7):1124-1137. doi: 10.1038/s41590-023-01519-9. Epub 2023 May 22.
The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (T) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that T cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of T cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that T cells support stromal cell responses to vaccines.
生发中心（GC）的规模和质量随年龄增长而下降，导致老年人疫苗诱导的免疫反应较差。功能性 GC 需要多种细胞类型在时间和空间上的协调，特别是在其两个功能不同的隔室：亮区和暗区。在老年小鼠中，存在趋化因子受体 4（CXCR4）介导的滤泡辅助性 T 细胞（Tfh）向暗区的定位错误，以及亮区滤泡树突状细胞（FDC）网络的压缩。在这里，我们表明 T 细胞的定位对于抗体反应的质量以及免疫接种后 FDC 网络的扩展至关重要。通过提供与 FDC 共定位的 T 细胞（使用趋化因子受体 5，CXCR5），纠正了老年小鼠中较小的 GC 和压缩的 FDC 网络。这表明 GC 反应中的年龄依赖性缺陷是可逆的，并表明 T 细胞支持基质细胞对疫苗的反应。
