Somatic Diversification of Immunoglobulin Genes in GALT

GALT 中免疫球蛋白基因的体细胞多样化

• 批准号: 6365774
• 负责人: Katherine L. Knight
• 金额: $ 29.97万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-05 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6365774
• 关键词: antibody formation; antigen receptors; bacteria; bacterial antigens; cell population study; chemical structure function; developmental immunology; enzyme linked immunosorbent assay; gene rearrangement; gene targeting; genetically modified animals; gut associated lymphoid tissue; host organism interaction; immunoconjugates; immunocytochemistry; immunogenetics; immunoglobulin genes; immunoregulation; laboratory mouse; laboratory rabbit; lymphocyte; microorganism population study; newborn animals; southern blotting; superantigens; thymectomy

DESCRIPTION (provided by applicant): The preimmune antibody repertoire plays an important role in immune protection because it is the initial repertoire that determines to which antigens an individual will respond. The forces that shape this repertoire however, are largely unknown and the goal of this project is to determine the extent to which intestinal microorganisms contribute to the preimmune antibody repertoire. In rabbits, the preimmune antibody repertoire is generated through a combination of Ig gene rearrangements in utero followed by somatic diversification of the Ig genes in gut-associated lymphoid tissues (GALT) between 3 and 6 weeks after birth. This somatic diversification of Ig genes is dependent on the intestinal micro flora. The goal of this project is to determine the mechanism by which the intestinal flora promotes stimulation of B cells and somatic diversification of Ig genes in GALT. The specific aims of this application are to: 1) Introduce individual bacterial species into a sterile GALT environment and identify an organism that induces B cell follicle formation and somatic diversification of Ig genes; 2) Use immunotoxins and soluble CTLA4 and CD4O to deplete T cell activity in vivo and determine if T cells are required for somatic diversification of Ig genes in GALT; 3) Develop transgenic rabbit with VH-truncated m-chain to determine whether the B cell receptor is required for GALT development and somatic diversification of Ig genes, and 4) Determine whether B cells are stimulated in GALT by antigen or a microbial superantigen, by using ELISA, in vitro stimulation assays and anti-hapten transgenic rabbits. These studies are important because they will begin to elucidate how commensal intestinal microflora affects the antibody repertoire and may be useful for designing mucosal vaccines.

描述（由申请人提供）：免疫前抗体曲目播放 在免疫保护中的重要作用，因为这是最初的曲目 确定一个人会反应哪些抗原。形状的力 然而，这个曲目在很大程度上是未知的，该项目的目标是 确定肠道微生物有助于多大程度 免疫前抗体库。 在兔子中，免疫前抗体库是通过A产生的 IG基因重排的结合，然后是体细胞 Ig基因在肠道相关淋巴组织（GALT）中的多样化 出生后3到6周之间。 Ig基因的体细胞多样化是 取决于肠道微菌群。这个项目的目标是 确定肠道菌群促进B的机制 GALT中Ig基因的细胞和体细胞多样化。 该应用的具体目的是：1）引入个体细菌 物种进入无菌galt环境，并鉴定出诱导B的生物 Ig基因的细胞卵泡形成和体细胞多样化； 2）使用 免疫毒素和可溶性CTLA4和CD4O在体内耗尽T细胞活性，并且 确定Ig基因在体细胞中是否需要T细胞 加尔特； 3）用VH截断的M链形成转基因兔以确定 B细胞受体是否需要Galt发育和体细胞。 Ig基因的多样化，以及4）确定B细胞是否在 通过抗原或微生物超抗原的galt，使用ELISA，体外 刺激测定法和抗Hapten转基因兔子。 这些研究很重要，因为它们将开始阐明如何共同 肠道菌群影响抗体库，可能对 设计粘膜疫苗。