B Cell Expansion After Dendritic Cell Immunization

描述(由申请人提供)：树突状细胞是免疫反应的有效和必要的启动者。这种特性已经开始被用于人类疾病和动物模型的实验使用。尽管许多关于树突状细胞与T和B细胞相互作用的本质的信息正在被曝光，但这仍然是一个快速发展的领域。使用标记稳定的培养树突状细胞，供体细胞在静脉注射后在体内持续存活和扩张。这些正在扩张的细胞被鉴定为B细胞，它在骨髓来源的树突状细胞中代表了一小部分(1%)受污染的群体，但在树突状细胞转移到动物体内后，它们显著地扩张。将进行实验，以确定树突状细胞与B细胞相互作用的性质，这种相互作用允许这些B细胞在体外和体内存活和增殖。具体地说，抗原在这一现象中的作用将被剖析。这种供体B细胞扩增对并发T细胞反应的潜在影响也将被检测。Kappler/Marack实验室是开始研究事业的理想和刺激的环境。这个实验室，以及科罗拉多大学社区和儿科系一直非常支持我作为一名内科科学家开始成功职业生涯的目标。作为一名儿科血液学家/肿瘤学家，我有幸在一个与基础科学密切相关的领域工作，这个领域将从翻译工作中受益匪浅。我近期的职业道路将包括持续的基础研究和学习，以提高我最终的科学生产力。

DESCRIPTION (provided by applicant): Dendritic cells are potent and essential initiators of immune responses. This quality has begun to be harnessed for experimental use in human disorders and animal models. Though much information is coming to light about the nature of dendritic cell interactions with T and B cells, this remains a rapidly evolving field. Using stably marked, cultured dendritic cells, persistent survival and expansion of donor cells have been noted in vivo after I.V. administration. These expanding cells have been identified as B cells which represent a small (1 %) contaminating population in bone marrow derived dendritic cells, but which expand significantly after dendritic cell transfer to animals. Experiments will be performed to determine the nature of dendritic cell-B cell interactions which allow for both the survival and proliferation of these B-cells in vitro and in vivo. Specifically, the role of antigen will be dissected in this phenomenon. The potential impact of this donor B-cell expansion on concurrent T cell responses will be examined as well. The Kappler/Marrack laboratory is an ideal and stimulating environment in which to launch a research career. This laboratory, as well as the University of Colorado community, and the Department of Pediatrics have been very supportive of my goal to initiate a successful career as a physician scientist. As a pediatric hematologist/oncologist , I have the good fortune of working in a field that is tied closely to the basic sciences, and one that will benefit greatly from translational endeavors. My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity.