Human Memory B cells in Humanized Mice

描述（由申请人提供）：记忆细胞难以在人类受试者中进行功能定义。已经接受人胸腺和胎肝植入物的人源化小鼠产生人免疫系统，并自发地响应内源性和环境抗原，以产生具有假定IgM记忆/活化B细胞和类别转换记忆/活化B细胞表型的细胞。我们将使用免疫和BrdU标记策略来鉴定在延长的时间内保留BrdU标记的抗原特异性B细胞，以便在功能上定义人IgM记忆和类别转换记忆细胞。关于人IgM+ CD 27 + B细胞起源的争议也可能在人源化小鼠的类似研究中得到解决。 公共卫生相关性：定义和理解人类记忆B细胞的起源将有助于开发新的和合理的疫苗生产方法。这些细胞也与许多人类B谱系恶性肿瘤有关，从淋巴瘤发生的角度来看，了解这些自然长寿的B细胞的生物学将是重要的。

DESCRIPTION (provided by applicant): Memory cells are difficult to functionally define in human subjects. Humanized mice that have received implants of human thymus and fetal liver generate a human immune system and spontaneously respond to endogenous and environmental antigens to generate cells with the phenotype of presumed IgM memory/activated B cells and class-switched memory/activated B cells. We will use an immunization and BrdU labeling strategy to identify antigen-specific B cells that retain BrdU label over extended periods in order to functionally define human IgM memory and class-switched memory cells. Controversies regarding the origins of human IgM+CD27+ B cells may also be resolved in similar studies on humanized mice. PUBLIC HEALTH RELEVANCE: Relevance Defining and understanding the origins of human memory B cells will help the development of novel and rational approaches for vaccine generation. These cells are also linked to a number of human B lineage malignancies and understanding the biology of these naturally long-lived B cells will be of importance from a lymphomagenesis standpoint.