Impaired selection of germinal centre B cells in ageing diminishes the quality of antibody mediated immunity upon vaccination

现代社会的主要成就之一是人类寿命的延长。随之而来的人口老龄化对科学提出了挑战，即了解老龄化过程以促进健康老龄化。随着年龄的增长，我们在感染后更有可能出现健康状况不佳的情况。可悲的是，2019冠状病毒病大流行证明了这一点，老年人更有可能在感染后住院和/或死亡。疫苗接种目前是预防传染病最有效的方法，但在我们的一生中，免疫系统的变化意味着老年人受到疫苗的保护往往不如年轻人。大多数疫苗通过刺激B细胞（一种白细胞）产生抗体来起作用，这种抗体可以有效地中和病原体并阻止感染的发生。为了在接种疫苗后产生有效的抗体反应，B细胞需要与称为生发中心的中心中的其他免疫细胞相互作用。在生发中心内，B细胞接受来自T细胞（另一种白细胞）和其他邻近细胞的指令，这些细胞提供结构和生存信号。这些指示有助于提高抗体对疫苗的反应质量，在接种疫苗后产生长期、高质量的抗体反应。在老年人中，接种疫苗后形成的生发中心较小，来自这些中心的抗体反应的质量比年轻人差。该项目将调查衰老是否会损害T细胞和结构细胞向B细胞传递适当指令，或者年老的B细胞是否无法在生发中心得到适当的教育。从这项研究中，我们将理解为什么老年人更容易对疫苗产生低质量的抗体反应。我们的目标是利用这方面的知识，为未来在老年人身上更有效的疫苗接种策略提供信息，以促进整个生命周期的健康。

One of the major achievements of the modern era is the extension of the human lifespan. The consequent shift towards older populations creates a challenge for science, to understand the ageing process in order to facilitate healthy ageing. As we age, we are more likely to have poor health outcomes after infection. This, sadly, has been demonstrated by the COVID-19 pandemic with older people more likely to be hospitalised and/or die after infection. Vaccination is currently the most effective way to prevent infectious disease, but changes in the immune system over our lifetimes mean that older people are often less well protected by vaccines than younger people. Most vaccines work by stimulating B cells, a type of white blood cell, to produce antibodies that can effectively neutralise pathogens and stop an infection in its tracks. To generate potent antibody responses upon vaccination, B cells need to interact with other immune cells in hubs called germinal centres. Within germinal centres, B cell receive instructions from both T cells, another type of white blood cell, and other neighbouring cells that provide structure and survival signals. These instructions help improve the quality of the antibody response to the vaccine, creating a long-lived, high quality antibody response after vaccination. In older individuals, the germinal centres that form upon vaccination are smaller and the quality of the antibody response that comes from these hubs is poorer than in younger individuals. This project will investigate whether ageing impairs the delivery of appropriate instructions from T cells and structural cells to B cells, or whether older B cells are unable to be properly educated in the germinal centre. From this research, we will understand why older individuals are more likely to have a poor-quality antibody response to vaccination. It is our aim to use this knowledge to inform future vaccination strategies that are more effective in older bodies in order to promote health across the lifespan.