ROLE OF APPENDIX AND GALT IN DEVELOPMENT OF THE PRIMARY HUMAN IMMUNE REPERTOIRE

附录和 GALT 在人类初级免疫库发育中的作用

• 批准号: 6160754
• 负责人: R G MAGE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160754
• 关键词: B lymphocyte; antibody formation; autoimmunity; cell differentiation; child (0-11); developmental immunology; gut associated lymphoid tissue; human subject; ileocolonic region; immunocytochemistry; laboratory rabbit; polymerase chain reaction; tissue /cell culture

We have been studying the rabbit appendix and find that it is an important site of development of the cells destined to produce protective antibodies. In the young rabbit, there is rapid growth and expansion of B lymphocytes in the appendix, and positive and negative selection events appear to occur within this organ. Because of the remarkable finding that the developing rabbit appendix is a site of repertoire diversification and selection, we are extending our findings from the rabbit model to studies of the developing human immune system. We are initiating investigations aimed at determining whether the human appendix or other Gut Associated Lymphoid Tissues (GALT) are important sites of early events in human B cell development, diversification and selection. In addition we are asking whether appendix functions in the diversification of the antibody repertoire during repopulation of other lymphoid organs, if the repertoire diversity or B-lymphocyte numbers of these organs are reduced by a genetic defect, irradiation or chemotherapy. Studies of human embryonic development show that the distal midgut and ileocecal portion of the digestive system, including the appendix, are developmentally homologous with the bursa of Fabricius. In view of our new findings in the rabbit model that indicate that the rabbit appendix has functions similar to the avian bursa, we believe it is important to conduct a new evaluation of the role of human GALT in development of the human immune repertoire and mucosal immunity.

我们一直在研究兔子的阑尾，发现它是一种 细胞发育的重要场所注定要产生 保护性抗体。在幼兔体内，有快速生长和 阑尾B淋巴细胞扩张，阳性和阴性 选择事件似乎发生在这个器官内。因为 惊人的发现是发育中的兔阑尾是 曲目多样化和选择，我们正在扩大我们的发现 从兔子模型到人类免疫系统发育的研究。 我们正在展开调查，目的是确定人类是否 阑尾或其他肠道相关淋巴组织(GALT)很重要 人类B细胞发育、多样化和早期事件的地点 选择。此外，我们还在询问附录是否在 其他血吸虫种群中抗体库的多样性 淋巴器官，如果曲目多样性或B淋巴细胞数量 这些器官因遗传缺陷、辐射或 化疗。对人类胚胎发育的研究表明， 消化系统的远端中肠和回盲部，包括 阑尾，在发育上与法氏囊同源。 法布里修斯。鉴于我们在兔模型中的新发现， 说明兔的阑尾具有与禽类相似的功能 Bursa，我们认为重要的是对 人类GALT在人类免疫谱系发展中的作用 粘膜免疫。