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 具体目标。 (1)以确定是否减少 老年小鼠中B细胞库的多样性是由受损的 在中枢（骨髓）中形成多样化的库，和/或 外周淋巴（脾和淋巴结）组织。 他们将使用一个 新的基于PCR的方法来测量IG CDR 3大小的异质性， 分析B细胞库的多样性和 3、12和18月龄小鼠中的克隆B细胞群。 他们将 还分析抗H-2抗体中体细胞突变的频率 在给予同基因t细胞的RAG-1缺陷小鼠中作为转基因表达 分别来自3、12和18个月大的小鼠。 最后，他们应确定 观察到的单克隆B细胞扩增的免疫学后果， 老年小鼠的免疫反应。 (2)制定战略， 老年小鼠B细胞发育和体细胞突变的限制。 他们将测试免疫球蛋白转基因的能力， 诱导型RAG基因使老年小鼠的B细胞发育正常化。 他们 还将确定来自年轻小鼠或TCP-17的T细胞是否可以 克服了报道的老年小鼠T细胞受损的能力， 支持转基因在缺乏RAG环境中体细胞突变。 最后，他们将测试TCP-17增加RAG基因的能力。 表情 VDJ重排以及 在老年小鼠中产生外周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.