Regulation of Local B Cell Responses to Influenza Under Conditions of Infection,

流感病毒对人类健康构成重大威胁。它也容易引起双重感染 呼吸道（RT），最常见的是肺炎链球菌，并负责 .发病率和死亡率很高，特别是在年轻人和老年人中。B细胞在 对流感病毒的免疫力，突出表现为产生病毒中和抗体， 流感疫苗的有效性。尽管认识到B细胞在宿主中起关键作用 尽管人们对流感病毒的免疫应答存在差异，但对流感病毒中保护性体液应答的性质知之甚少。 我们的项目提出全面分析和比较B细胞反应， 在病毒感染的情况下，同时伴有或不伴有细菌共感染， 就像疫苗一样。 我们假设B细胞对流感病毒的应答在不同的免疫应答中有不同的特征。 这些不同的背景。重点将放在本地RT免疫功能， 促进抗流感B细胞存活、成熟和分化。我们还将确定 调节浆细胞（PC）发育、募集和维持的机制 RT.虽然短期PC可能会参与主机的快速第一线防御，但长期PC和 记忆细胞对于持久保护的发展至关重要。通过定义抗流感病毒 在病毒感染肺上皮细胞的原位反应中，我们可能更好地诱导 通过接种疫苗进行针对性粘膜保护。

Influenza virus poses a major threat to human health. It also predisposes to superinfection of the respiratory tract (RT), most commonly by Streptococcus pneumonia, and is responsible for . significant morbidity and mortality, particularly in the young and elderly. B cells play a vital role in immunity to influenza virus, highlighted by the production of viral-neutralizing antibodies and in the efficacy of influenza vaccines. While it is appreciated that B cells play a critical role in the host response to influenza virus, less is known about the nature of the protective humoral response in the RT. Our project proposes to comprehensively analyze and compare the B cell response in the lung to influenza virus under conditions of viral infection with or without bacterial co-infection as well as vaccination. We hypothesize that the B cell response to influenza virus will have distinct signatures in these divergent contexts. Emphasis will be placed on features of the local RT immunity that promote anti-influenza B cell survival, maturation and differentiation. We will also identify the mechanisms that govern the development, recruitment and maintenance of plasma cells (PC) in the RT. While short-term PC may participate in rapid first line of host defense, long-term PCs and memory cells are critical for the development of lasting protection. By defining the anti-influenza response in situ where the virus infects lung epithelial cells, we may be better equipped to induce targeted mucosal protection through vaccination.