The role of B cell - macrophage interactions for adaption to virus escape, memory, and immune tolerance

B 细胞-巨噬细胞相互作用在适应病毒逃逸、记忆和免疫耐受中的作用

• 批准号: BB/X017281/1
• 负责人: Kai-Michael Toellner
• 金额: $ 84.92万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX017281%2F1
• 关键词: role; cell; macrophage; interactions; adaption

Vaccination induces antibodies that protect us from infection for many years. The same happens during infection. We try to understand how our immune system is able to custom design antibodies that can exactly fit to any random infectious agents we might come into contact with. Antibodies are generated by B cells. The process of B cells adapting to foreign structures on infectious agents happens in lymph nodes and is called B cell affinity maturation. Affinity maturation takes several weeks, which is why vaccination takes weeks to fully protect us. We recently found that another cell type is important in the process of B cell affinity maturation: phagocytic "eating" cells that can filter and eat infectious agents in the lymph and blood stream. These phagocytes can transfer what they see to B cells, and in this way alert B cells of any new threats emerging. We found that the first thing B cells do after affinity maturation is to interact with phagocytes. It seems that B cells test whether they recognise any of what the phagocytes are carrying. We think this is a very important 1st check to test whether freshly affinity-matured B cells are useful in the long term. In the current project we plan to better characterise what exactly happens during the interaction of phagocytes and B cells. Which signals can and do phagocytes transfer to B cells? Further, we want to test why this interaction is so important. We think there are several possible explanations: 1) The interaction of phagocytes and B cells can alert B cells that the infectious agent has mutated. This is common in virus infections, e.g. the Covid-19 virus, influenza, or HIV infection. 2) Phagocytes may tell B cells that the infectious agent is still around and instruct them to keep going with affinity maturation, making affinity maturation more efficient. 3) The interaction may alert B cells that they react with structures that are part of the healthy body - self. These self-reactive B cells must be deleted or instructed to affinity-mature away from self-reactivity in order to prevent illness from self-reactive antibody. 4) The interaction may be important to quickly instruct B cells to make protective antibodies.We plan to test all these possible scenarios. The project should lead to understanding how our immune system deals efficiently with infection and vaccination, how we deal with virus mutants and why during the process we do not become autoimmune to ourselves. Apart from answering these basic questions of biological process, understanding them should help to generate better vaccines or drugs that stimulate our bodies' immune response to infectious agents.

接种疫苗会产生抗体，保护我们多年免受感染。感染时也是如此。我们试图了解我们的免疫系统如何能够定制设计抗体，这些抗体可以完全适合我们可能接触到的任何随机传染因子。抗体由B细胞产生。B细胞适应感染因子上的外来结构的过程发生在淋巴结中，称为B细胞亲和力成熟。亲和力成熟需要几周时间，这就是为什么接种疫苗需要几周时间才能完全保护我们。我们最近发现，另一种细胞类型在B细胞亲和力成熟过程中很重要：吞噬“进食”细胞，可以过滤和吃掉淋巴液和血流中的感染因子。这些吞噬细胞可以将它们所看到的转移到B细胞，并以这种方式警告B细胞任何新的威胁出现。我们发现B细胞在亲和力成熟后做的第一件事就是与吞噬细胞相互作用。似乎是B细胞测试它们是否识别吞噬细胞携带的任何东西。我们认为这是一个非常重要的第一次检查，以测试新鲜的亲和力成熟的B细胞是否在长期内有用。在目前的项目中，我们计划更好地了解吞噬细胞和B细胞相互作用期间到底发生了什么。吞噬细胞可以传递哪些信号给B细胞？此外，我们想测试为什么这种相互作用如此重要。我们认为有几种可能的解释：1）吞噬细胞和B细胞的相互作用可以提醒B细胞感染因子已经发生突变。这在病毒感染中很常见，例如Covid-19病毒、流感或HIV感染。2)吞噬细胞可以告诉B细胞，感染因子仍然存在，并指示它们继续进行亲和力成熟，使亲和力成熟更有效。3)这种相互作用可能会提醒B细胞，它们与健康身体-自我的一部分结构发生反应。这些自身反应性B细胞必须被删除或指导亲和力成熟远离自身反应性，以防止疾病的自身反应性抗体。4)这种相互作用可能对快速指导B细胞产生保护性抗体很重要。我们计划测试所有这些可能的情况。该项目将有助于了解我们的免疫系统如何有效地处理感染和疫苗接种，我们如何处理病毒突变体，以及为什么在这个过程中我们不会对自己产生自身免疫反应。除了回答这些生物过程的基本问题外，了解它们还有助于产生更好的疫苗或药物，刺激我们身体对传染性病原体的免疫反应。