THE EFFECT OF AGE ON THE GENERATION OF A DIVERSE B-CELL REPERTOIRE

描述：(改编自应用程序)：该项目具有 遵循特定的目标。(1)确定是否减少了 老年小鼠B细胞库的多样性是由受损的小鼠造成的 在中央(骨髓)和/或发展不同的曲目 外周淋巴(脾和淋巴结)组织。他们将使用一个 一种检测免疫球蛋白CDR3大小异质性的新方法 检测B细胞库的多样性和B细胞的出现情况 3月、12月和18月龄小鼠的克隆性B细胞群。他们会 我还分析了抗H-2抗体的体细胞突变频率 在给予同基因t细胞的RAG-1缺陷小鼠中表达为转基因 取自3月龄、12月龄和18月龄的小鼠。最后，他们应确定 观察到的单克隆性B细胞扩张的免疫学后果 上了年纪的老鼠对免疫反应。(2)制定战略，克服 老年小鼠B细胞发育和体细胞突变的制约因素。 他们将测试免疫球蛋白转基因的能力，以及 诱导RAG基因使老龄小鼠B细胞发育正常化。他们 也将确定来自幼鼠或TCP-17的T细胞是否可以 克服报道的老年小鼠T细胞能力受损的情况 支持在RAG缺乏的环境中进行转基因的体细胞突变。 最后，他们将测试TCP-17增加RAG基因的能力 表情。VDJ的重排以及 在老年小鼠体内产生外周B细胞。

DESCRIPTION: (adapted from the application): The project has the following specific aims. (1) To determine whether the decreased diversity of the B cell repertoire in old mice results from the impaired development of a diverse repertoire in the central (bone marrow) and/or peripheral lymphoid (spleen and lymph nodes) tissues. They will use a novel PCR-based method to measure the heterogeneity of Ig CDR3 sizes to assay the diversity of the B cell repertoire and the appearance of clonal B cell populations in 3, 12, and 18 month old mice. They will also analyze the frequency of somatic mutations in an anti-H-2 antibody expressed as a transgene in RAG-1 deficient mice given syngeneic t cells from 3,12, and 18 month old mice. Finally, they shall determine the immunological consequences of monoclonal B cell expansions observed in old mice on the immune response. (2) To develop strategies to overcome the constraints in B cell development and somatic mutation in old mice. They will test the capacity of an immunoglobulin transgene, and inducible RAG genes to normalize B cell development in old mice. They will also determine whether T cells from young mice or TCP-17 can overcome the reported impaired capacity of T cells from old mice to support somatic mutation of transgene in a RAG-deficient environment. Finally, they will test the capacity of TCP-17 to increase RAG gene expression. VDJ rearrangement as well as the decreased rate of generating peripheral B cells in old mice.