Impact of Aging on Memory B Cell and Humoral Immunity with West Nile Virus

描述(申请人提供)：西尼罗河病毒(WNV)是一种新出现的蚊子传播的黄色病毒，可导致几种脊椎动物的致命脑炎。老年人特别容易受到西尼罗河病毒的感染，发病率和死亡率都有所增加。虽然老年人在接种候选抗病毒疫苗后往往不能产生保护性体液免疫反应，但其背后的机制原因却鲜为人知。事实上，关于形成B细胞中介记忆的与年龄相关的变化，我们知之甚少。与人类一样，老年小鼠在感染西尼罗河病毒后对严重疾病的易感性增加。为了了解这些观察的潜在机制，我们将评估成年(4-6个月大)和老年(18个月大)小鼠的B细胞谱系和功能。我们将比较成年和老年小鼠在感染西尼罗河病毒后记忆发育的大小和质量，以及在二次感染后的记忆反应。我们假设，老年小鼠对西尼罗河病毒感染会产生质量和数量都较低的B细胞介导的免疫反应，表现为中和抗体水平降低，抗体分泌细胞减少，最终在二次感染后记忆反应减弱。这项研究的结果将有助于我们理解导致体液反应免疫衰老的机制，并为老年人预防西尼罗河病毒和其他全球相关传染病的疫苗的开发奠定基础。

DESCRIPTION (provided by applicant): West Nile Virus (WNV) is an emerging mosquito-born flavivirus that can lead to fatal encephalitis in several vertebrate animal species. The elderly ar especially vulnerable to WNV infection with increased incidence of disease and death. Although it is well characterized that elderly humans often fail to mount protective humoral immune response after immunization with candidate antiviral vaccines, the mechanistic causes behind this are poorly understood. Indeed, little is known regarding the age-related changes which shape B cell-mediated memory. Like humans, aged-mice show increased susceptibility to severe disease after WNV infection. To understand the underlying mechanisms of these observations we will assess the B cell repertoire and function in adult (4-6 month of age) and old (>18 months) mice. We will compare the magnitude and quality of the memory development in adult and aged mice following WNV infection and the memory response following a secondary infection. We hypothesize that old mice will develop lower qualitative and quantitative B cell-mediated immune responses against WNV infections that manifests as reduced levels of neutralizing antibodies, fewer antibody secreting cells, and ultimately decreased memory responses following secondary infections. The results of this study should inform our understanding of the mechanisms leading to immunosenescence of the humoral response and frame the development of vaccines for the elderly against WNV and other globally relevant infectious diseases.