Protective functions of influenza-specific lung-resident memory B cells

项目总结 我们最近发现了一种新的流感特异性、驻留在肺部的记忆B细胞(BRM细胞)，它们是 表型不同于系统记忆B细胞，驻留在肺中的独特位置，反应更快 来挑战感染，而不是系统性感染。有趣的是，肺BRM细胞提供了显著程度的 即使它们不与猪瘟病毒的HA和NA蛋白发生交叉反应，也能保护机体免受感染 攻击病毒，这表明BRM细胞在产生抗体(Ab)之外还有额外的效应功能。 事实上，B细胞产生炎症细胞因子，如干扰素、淋巴毒素、OX40L和IL-6，以及抗炎 IL-10、IL-27和IL-35等细胞因子。此外，它们是有效的APC，特别是对于它们的同源抗原。 因此，除了抗体外，BRM细胞还具有多种机制来调节炎症和促进抗炎。 病毒免疫。这项计划中的实验将研究流感特异性BRM细胞使用的机制 清除病毒和保护肺部，并将决定肺部疫苗接种如何引发和维持BRM 肺里的细胞。

PROJECT SUMMARY We recently identified a novel population of flu-specific, lung-resident memory B cells (BRM cells) that are phenotypically different than systemic memory B cells, reside in unique sites in the lung and respond more rapidly to challenge infection than their systemic counterparts. Interestingly, lung BRM cells provide a significant degree of protection to challenge infection, even when they do not cross-react with the HA and NA proteins of the challenge virus, suggesting that BRM cells have additional effector functions beyond antibody (Ab) production. In fact, B cells make inflammatory cytokines like IFN, lymphotoxin, OX40L and IL-6, as well as anti-inflammatory cytokines like IL-10, IL-27 and IL-35. Moreover they are potent APCs, particularly for their cognate antigens. Thus, BRM cells have a variety of mechanisms, in addition to Ab, to modulate inflammation and promote anti- viral immunity. The experiments in this proposal will investigate the mechanisms used by flu-specific BRM cells to clear virus and protect the lung and will determine how pulmonary vaccination can elicit and maintain BRM cells in the lung.