RUI: Understanding Repertoire Diversification in a Nonstandard Model

9723569 Goldsby这个项目正在研究牛的一次抗体库的开发。在牛的回肠皮耶氏区(IPP)，一种肠道相关的淋巴组织，是B细胞多样化的主要部位。靶向的、发育调节的体细胞点突变过程是IPP多样性产生的原因。然而，这并不是牛多样化的唯一部位或机制，因为在胎儿发育过程中，脾已被证明是轻链多样化的部位。此外，这位研究人员有数据表明，重链V基因重排(但不是轻链)发生在骨髓中。因此，对牛B细胞的发育提出如下假说：1)在胚胎骨髓中发生重链重排而不是轻链重排；2)重链基因重排的细胞迁移到脾，在那里重链重排；3)Peyer‘s斑状卵泡种植从胎儿脾中经历了多样化的池中的B细胞。将进行实验来验证这一假设。这些结果将提供有关牛抗体多样性如何发展的信息，并将表明物种在多样性产生过程中的差异。这笔助学金来自瑞县一所学院，本科生将参与这项研究。尽管所有高等脊椎动物都有相似的免疫系统，由调节免疫反应的B细胞和T细胞产生的抗体组成，但生物产生具有不同特异性的抗体的机制在所有物种中并不相同。该项目中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. ***