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

项目摘要 我们最近发现了一种新的流感特异性肺部记忆B细胞（BRM细胞）， 表型上不同于全身记忆B细胞，存在于肺中的独特部位，反应更迅速 更能对抗感染有趣的是，肺BRM细胞提供了显著程度的 保护挑战感染，即使当他们不交叉反应的HA和NA蛋白的 攻击病毒，表明BRM细胞具有除抗体（Ab）产生之外的额外效应子功能。 事实上，B细胞产生炎性细胞因子如IFN γ、光氧合酶、OX40 L和IL-6，以及抗炎性细胞因子。 细胞因子如IL-10、IL-27和IL-35。此外，它们是有效的APC，特别是对于它们的同源抗原。 因此，BRM细胞除了Ab外，还具有多种机制来调节炎症并促进抗肿瘤作用。 病毒免疫本实验将研究流感特异性BRM细胞的作用机制 以清除病毒和保护肺部，并将确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.