MURINE B LYMPHOCYTE DEVELOPMENT

本研究项目的目的是检查 淋巴细胞生成祖细胞以产生某些抗原反应性B细胞 过继转移中的子集。 一种新的移植模型将是 涉及未照射的免疫缺陷xid小鼠， 以产生抗磷酸胆碱（PC）PFC反应。 通过使用未经辐照的 宿主，移植的供体细胞和宿主细胞之间的强制竞争， 完整的宿主细胞发育成成熟状态的机会 应该接近个体发育的正常情况;通过研究 干细胞分化在相对正常的，或非破坏性的， 条件下，即使是再生能力之间的细微差别， 不同抗原反应性亚群的前体将被加重。 因此，该实验系统提供了一种灵敏的分析手段， 新兴B细胞亚群的群体动力学。 此外，由 利用PC系统，能够根据 显性和非显性独特型将提供额外水平的 歧视 将干细胞移植到 最低限度地改变环境，并监测相关的， 特异性定义明确的抗原反应性亚群， 移植的细胞将不仅提供关于生成的信息， B细胞谱系的多样化，而且关于克隆 在功能上划定的B细胞区室内的关系。 我们 我相信我们的实验将提供新的信息， 异常小鼠淋巴细胞生成

The purpose of this research project is to examine the capacities of lymphopoietic progenitors to generate certain antigen-reactive B cell subsets in adoptive transfer. A novel transplantation model will be employed involving unirradiated immunodeficient xid mice which are unable to mount anti-phosphorylcholine (PC) PFC responses. By using unirradiated hosts, the forced competition between the engrafted donor cells and the intact host cells for the opportunity to develop into the mature state should closely approximate the normal situation in ontogeny; by studying stem cell differentiation under relatively normal, or nondisruptive, conditions, even subtle distinctions between the regeneration abilities of precursors to different antigen-reactive subsets will be accentuated. Thus, the experimental system offers a sensitive means for analyzing the population dynamics of emerging B cell subpopulations. Furthermore, by utilizing the PC system, the ability to partition responses in terms of dominant and nondominant idiotypes will provide an additional level of discrimination. The transplantation of stem cells into precisely and minimally altered environments, and the monitoring of the related, idiotypically well-defined antigen-reactive subsets generated by the engrafted cells will provide information not only on the generation and diversification of B cell lineages, but also with respect to the clonal relationships within functionally delineated B cell compartments. We believe that our experiments will provide new information on normal and abnormal murine lymphopoiesis.