Asymmetric Lymphocyte Division in the Immune Response

描述（由申请人提供）：B淋巴细胞及其产生的抗体在宿主防御微生物和自身免疫性疾病中起关键作用。适应性免疫的一个标志是抗原经历的B细胞命运的异质性。大量的初步数据表明，B细胞可以通过一种进化保守的策略来分配不相等数量的关键成分，从而使它们的子细胞的命运和功能多样化。该项目将测试不对称细胞分裂是否是早期B细胞介导的免疫反应的主要特征。目的是研究是否存在一种确定性机制来多样化兄弟B细胞的初始类别切换选择，以及不对称分裂是否用于满足终端分化和自我更新的相反需求。该项目还将研究细胞极性的祖先调节因子是否负责建立非对称分裂所需的细胞生物学特征，以及非对称遗传蛋白如何介导子B细胞的命运差异。这些研究应该为免疫反应的合理工程和针对微生物剂的疫苗提供一个框架，并解决有关淋巴细胞克隆选择原则的基本不确定性，以应对传染病或在我们的免疫细胞攻击我们自己的情况下。

DESCRIPTION (provided by applicant): B lymphocytes and the antibodies they produce play a critical role in host defense against microbes and in autoimmune diseases. A hallmark of adaptive immunity is heterogeneity of cell fate among antigen-experienced B cells. Substantial preliminary data suggest B cells can diversify the fates and functions of their daughter cells using an evolutionarily conserved strategy to allocate unequal amounts of key components. This project will test whether asymmetric cell division is a cardinal feature of the early B cell-mediated immune response. The aims will examine whether a deterministic mechanism is used to diversify the initial class switch choices of sibling B cells, and whether asymmetric division i used to meet the opposing demands of terminal differentiation and self-renewal. This project will also examine whether ancestral regulators of cell polarity are responsible for establishing cell biological features necessary for asymmetric division, and how asymmetrically inherited proteins could mediate fate disparity in daughter B cells. These studies should provide a framework for rational engineering of immune responses and vaccines against microbial agents and address fundamental uncertainties regarding the principle of clonal selection of lymphocytes in response to infectious diseases or during situations when our immune cells attack our own selves.