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。它也容易发生双重感染。 呼吸道(RT)，最常见的是肺炎链球菌，并负责 。严重的发病率和死亡率，特别是在年轻人和老年人。B细胞在多种疾病中起着至关重要的作用 对流感病毒的免疫力，突出表现为产生病毒中和抗体和在 流感疫苗的效力。虽然可以理解B细胞在宿主中起着关键作用 对于流感病毒的反应，人们对保护性体液反应的性质知之甚少 The RT.我们的项目建议全面分析和比较B细胞反应在 在有或没有细菌混合感染的情况下，肺对流感病毒的影响 作为疫苗接种。 我们假设B细胞对流感病毒的反应将在 这些不同的背景。重点将放在局部RT免疫的特征上， 促进抗流感B细胞存活、成熟和分化。我们还将确定 控制浆细胞(PC)的发育、招募和维持的机制 RT.虽然短期PC可能参与主机防御的快速第一线，但长期PC和 记忆细胞对持久保护的发展至关重要。通过定义抗流感 在病毒感染肺上皮细胞的地方，我们可能更有能力诱导 通过接种疫苗进行有针对性的粘膜保护。

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.