RUI: Understanding Repertoire Diversification in a Nonstandard Model

9723569 Goldsby这个项目正在研究牛一抗库的开发。牛的回肠Peyer’s patch （IPP）是一种肠道相关的淋巴组织，是B细胞分化的主要部位。一个有针对性的、受发育调控的体细胞点突变过程负责IPP多样性的产生。然而，这并不是牛多样化的唯一部位或机制，因为脾脏已被证明是胎儿发育过程中轻链多样化的一个部位。此外，该研究人员的数据表明，重链V基因重排（而不是轻链）发生在骨髓中。因此，对牛B细胞的发育提出以下假设：1)在胎儿骨髓中发生重链重排，而不是轻链重排；重链基因重排的细胞迁移到轻链重排的脾脏；(3)Peyer’s patch follicle植入来自胎儿脾脏中分化的B细胞池。将进行实验来验证这一假设。这些结果将提供有关牛体内抗体多样化如何发展的信息，并将表明多样性产生的物种差异。本研究经费由一所RUI学院提供，研究对象为本科生。尽管所有高等脊椎动物都有相似的免疫系统，由B细胞和T细胞产生的抗体组成，这些抗体调节免疫反应，但生物体产生不同特异性抗体的机制在所有物种中并不相同。该项目的实验将提供有关牛体内各种抗体发展的信息。* * *

9723569 Goldsby This project is studying the development of the primary antibody repertoire in cattle. In cattle the ileal Peyer's patch (IPP), a gut associated lymphoid tissue, is a major site of B cell diversification. A process of targeted, developmentally regulated somatic point mutation is responsible for the generation of diversity in the IPP. However, this is not the sole site or mechanisms for diversification in cattle, since the spleen has been shown to be a site of light chain diversification during fetal development. Also, this investigator has data suggesting that heavy chain V gene rearrangement (but not light chain) occurs in the bone marrow. Thus the following hypothesis is proposed for the development of B cells in cattle : 1)In the fetal bone marrow rearrangement of heavy but not light chain occurs; 2)Cells with rearranged heavy chain genes migrate to the spleen where light chains rearrange; 3)Peyer's patch follicles are seeded with B cells from a pool that has undergone diversification in the fetal spleen. Experiments will be done to test this hypothesis. These results will provide information on how antibody diversification develops in cattle, and will indicate species differences in the generation of diversity. This grant is from a RUI college, and undergraduate students will be involved in this research. %%% Although all higher vertebrates have similar immune systems consisting of antibodies produced by B cells and T cells which modulate the immune response, the mechanism by which organisms generate antibodies with different specificities is not the same in all species. The experiments in this project will provide information on the development of diverse antibodies in cattle. ***