Central and Effector B cells in the Lung

描述(由申请人提供)：B细胞记忆--被定义为抗原特异的B细胞和浆细胞，长期保持--对于大多数当前疫苗的成功是必不可少的，包括流感疫苗。然而，我们对这些细胞是如何以及在哪里产生和维护的理解是不完整的。因此，很难合理地设计新的疫苗来有效地激发B细胞的记忆，或者干预记忆B细胞导致疾病的情况。尽管记忆B细胞在人类中已被识别出表型，但它们在小鼠中的对应细胞直到最近才更难识别。因此，虽然我们对记忆B细胞的样子有一些了解，特别是在人类血液中，但我们对组织中维持的记忆B细胞的了解要少得多。例如，记忆B细胞似乎维持在以前感染过流感的小鼠(可能还有人类)的肺中。然而，我们不知道这些记忆细胞与血液中循环的记忆细胞有什么不同。这项提议将确定中央记忆B细胞(在次级淋巴器官中)和效应记忆B细胞在外围非淋巴器官中的特征，如肺。我们还将确定维持肺中记忆B细胞和浆细胞的机制，确定记忆B细胞招募(或生成)到肺的时间，确定与其他部位相比，肺中记忆B细胞的特异性和寿命，并测试支气管炎相关淋巴组织(BALT)的存在是否改变肺中记忆B细胞的组成、寿命或活性。总而言之，这些实验将确定外周组织中维持的效应器记忆B细胞的表型，更重要的是确定其功能。因此，这些结果将为保护呼吸道的疫苗的合理设计提供信息，并导致增强或减少肺部记忆B细胞的产生和维持的治疗。

DESCRIPTION (provided by applicant): B cell memory - defined as antigen-specific B cells and plasma cells that are maintained over the long-term - is essential for the success of most current vaccines, including those to influenza. However, our understanding of how and where these cells are generated and maintained is incomplete. Thus, it is difficult to rationally design new vaccines that will efficiently elicit B cell memory or to intervene in situations in which memory B cells contribute to disease. Although memory B cells have been phenotypically identified in humans, their counterparts in mice have been, until recently, more difficult to identify. Thus, while we have some idea of what memory B cells look like, particularly in human blood, we have much less understanding of the memory B cells that are maintained in tissues. For example, memory B cells appear to be maintained in the lungs of mice (and presumably humans) that have been previously infected with influenza. However, we have no idea how these memory cells differ from their counterparts that circulate in the blood. This proposal will define the characteristics of central memory B cells (in secondary lymphoid organs) and effector memory B cells in peripheral non-lymphoid organs, such as the lung. We will also determine the mechanisms that maintain memory B cells and plasma cells in the lung, define the timing of memory B cell recruitment (or generation) to the lung, determine the specificities and longevity of the memory B cells in the lung compared to other sites and test whether the presence of Bronchus Associated Lymphoid Tissue (BALT) alters the composition, lifespan or activity of memory B cells in the lung. Together, these experiments will determine the phenotype and more importantly, the function of effector memory B cells that are maintained in peripheral tissues. Thus, these results will inform the rational design of vaccines that protect the respiratory tract and lead to therapies that enhance or curtail the generation and maintenance of memory B cells in the lung.