Role of memory B cell migration through the lymph node subcapsular sinus

疫苗接种规划是全球公共卫生战略的核心内容，是预防各种威胁生命感染的关键。疫苗如何诱导对细菌和病毒的免疫记忆仍然知之甚少。我们知道，接种疫苗和感染会诱导B细胞发生突变，并使它们的基因编码适应疫苗上所见的抗体结构。这些突变将导致产生高度特异性的抗体，可以中和细菌或病毒。在这个过程中也产生了长寿命的记忆B细胞，它将这些突变保存了很长时间。我们最近观察到，记忆B细胞不仅在体内传播并保存所遇到疫苗的信息，它们似乎还会收集所遇到的疫苗颗粒，并将它们运送回B细胞成熟的地方。这个项目的目的是了解为什么记忆B细胞进行这种抗原收集，以及哪些因素调节它。为了理解这种调节，我们将制造出不能产生一系列直接记忆B细胞迁移的受体的B细胞。为了了解抗原转运的功能，我们将破坏这一过程，并测试有效的B细胞成熟是否依赖于记忆B细胞持续的抗原收集和转运。老年人很难有效地对疫苗产生良好的抗体反应。在他们的B细胞成熟过程中看到的一些缺陷可能是由于记忆B细胞收集抗原的缺陷，我们计划测试这一过程是否在老年免疫系统中被破坏。这个项目的结果将有助于更好地理解疫苗如何诱导保护性免疫反应和记忆。我们可以更好地了解疫苗应该如何设计或交付。更好地理解为什么老年人对疫苗接种没有有效的反应，可能会导致如何纠正这一过程的想法。

Vaccination programmes are a core element of public health strategy worldwide and are key to preventing a wide range of life threatening infections. How vaccines induce immune memory to bacteria and viruses are still poorly understood. We know that vaccination and infection induces B cells to mutate and adapt their genes coding for antibody specific to structures seen on the vaccine. These mutations then will lead to the production of highly specific antibody that can neutralize bacteria or viruses. During this process are also long-lived memory B cells generated, which preserve these mutations for a long time.We recently observed that memory B cells not only spread through the body and preserve information on vaccines encountered, they also seem to harvest vaccine particles they encounter and transport them back to the places where B cells mature. The purpose of this project is to understand why memory B cells do this antigen harvest, and which factors regulate it. To understand the regulation, we will produce B cells that cannot produce a range of receptors that direct memory B cell migration. To understand the function of antigen transport, we will disrupt the process and test whether efficient B cell maturation is dependent on continued antigen harvest and transport by memory B cells. Aged people have problems efficiently producing good antibody responses to vaccines. Some of the defects seen during their B cell maturation may be due to a defect in antigen harvest by memory B cells, and we plan to test whether this process is disrupted in the aged immune system.Results from this project will help to better understand how vaccines induce protective immune responses and memory. We may better understand how vaccines should be designed or delivered. Better understanding why elderly do not react efficiently to vaccination may lead to ideas on how to correct this process.