Role Of Appendix and GALT In Development Of The Primary

附录和 GALT 在小学发展中的作用

• 批准号: 6506952
• 负责人: rose 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/6506952
• 关键词: B lymphocyte; antibody formation; autoimmunity; cell differentiation; developmental immunology; gut associated lymphoid tissue; human subject; human tissue; ileocolonic region; immunocytochemistry; laboratory rabbit; mucosal immunity; oral administration; polymerase chain reaction

Our studies in the rabbit have shown that the young appendix is an important site of development of the cells destined to produce protective antibodies. The rabbit appendix has functions similar to those of the avian bursa of Fabricius. In the young rabbit, there is rapid growth and expansion of B lymphocytes in the appendix, and positive and negative selection events occur. We believe that the cells that survive selection in the appendix seed the peripheral lymphoid system and undergo self renewal to maintain the primary repertoire. The data on rabbit led us to study the role of human appendix and GALT in development of the human immune repertoire and mucosal immunity. We compared development of normal human appendix germinal centers (GC) with rabbit appendix GC development at different ages. In both human and rabbit appendix, we found that lymphoid follicles were just beginning to form at birth. Germinal centers became evident at about 1 month in human and at 1 week in rabbit appendix. Most lymphoid development occurred within the first year in the human and within the first 12 weeks in the rabbit appendix. Lymphoid tissue began to atrophy by adulthood in both human and rabbit appendix. The follicles became smaller and fewer in number whereas the connective tissue and smooth muscle increased. The appendix did not entirely involute; germinal centers were still present in 5 human samples from individuals 75 years or older and in 6- and 7-year-old rabbit specimens. The human appendix shares some characteristics of a "mammalian bursa equivalent"; it is a B- cell rich organ in the young and the morphology of the follicles and GC changes with age. Although the human appendix is similar in many respects to the rabbit appendix and avian bursa, the GC structure and relative GC T-cell density differs. This could indicate that human appendix is more similar to a peripheral than central lymphoid organ. It is possible, however, that peripheral lymphoid organs share some central lymphoid function. Whether this is true for the human appendix and other GALT warrants further investigation (1). In order to further investigate whether the appendix of man plays any role as a primary lymphoid organ we microdissected single cells from normal human appendix tissues collected at 3 months, 4 years and 9 years of age for PCR amplification of rearranged VHDHJH genes, and direct DNA sequencing. Analyses of these sequences is in progress (see also Z01 AI00226-20 LI). We conducted a comparative study of single cell microdissection by hydraulic micromanipulation and laser capture microdissection (LCM) (2) and we are currently evaluating the Leica UV laser microdissection system (LMD ).

我们对兔子的研究表明，幼小的阑尾是产生保护性抗体的细胞的重要发育部位。兔子阑尾的功能与鸟类法氏囊相似。在幼兔中，阑尾中的 B 淋巴细胞快速生长和扩增，并发生正选择和负选择事件。我们相信，在阑尾选择中存活下来的细胞会播种到外周淋巴系统，并进行自我更新以维持主要的功能。兔子的数据使我们研究了人类阑尾和 GALT 在人类免疫库和粘膜免疫发育中的作用。我们比较了不同年龄时正常人阑尾生发中心（GC）的发育与兔阑尾GC的发育。在人和兔子的阑尾中，我们发现淋巴滤泡在出生时才刚刚开始形成。人类的生发中心在大约 1 个月时变得明显，而兔子的阑尾则在 1 周时变得明显。大多数淋巴样发育发生在人类的第一年和兔子阑尾的前 12 周内。人类和兔子的阑尾中的淋巴组织在成年后开始萎缩。卵泡变小，数量减少，而结缔组织和平滑肌却增加。阑尾未完全内卷； 75 岁或以上个体的 5 个人类样本以及 6 岁和 7 岁兔子样本中仍然存在生发中心。人类阑尾具有“哺乳动物法氏囊等效物”的一些特征；它是年轻人中富含 B 细胞的器官，卵泡和 GC 的形态随着年龄的增长而变化。尽管人类阑尾在许多方面与兔阑尾和禽类法氏囊相似，但 GC 结构和相对 GC T 细胞密度不同。这可能表明人类阑尾更类似于外周淋巴器官，而不是中央淋巴器官。然而，外周淋巴器官可能具有某些中枢淋巴功能。这对于人类阑尾和其他 GALT 是否属实，值得进一步研究 (1)。为了进一步研究人类阑尾是否发挥着作为主要淋巴器官的作用，我们对 3 个月、4 岁和 9 岁时收集的正常人类阑尾组织中的单细胞进行了显微解剖，用于重排 VHDHJH 基因的 PCR 扩增，并直接进行 DNA 测序。这些序列的分析正在进行中（另请参见 Z01 AI00226-20 LI）。我们对液压显微操作和激光捕获显微切割 (LCM) 进行单细胞显微切割进行了比较研究 (2)，目前我们正在评估徕卡紫外激光显微切割系统 (LMD)。