Role Of Appendix and GALT In Development Of The Primary

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发育的重要部位。兔子的阑尾具有类似于鸟类法氏囊的功能。在幼兔体内，阑尾B淋巴细胞快速生长和扩增，并发生阳性和阴性选择事件。我们认为，在阑尾的选择中存活下来的细胞为外周淋巴系统播下种子，并进行自我更新以维持主要的储备。根据家兔的实验数据，我们研究了人阑尾和GALT在人免疫库和粘膜免疫发育中的作用。我们比较了不同年龄正常人阑尾生发中心（GC）和兔阑尾生发中心的发育情况。在人类和兔子的阑尾中，我们发现淋巴滤泡在出生时才刚刚开始形成。生发中心在人类阑尾约1个月时和兔阑尾1周时变得明显。大多数淋巴细胞的发育发生在人类阑尾的第一年和兔阑尾的前12周。人和兔的阑尾淋巴组织在成年后开始萎缩。卵泡变小，数量减少，结缔组织和平滑肌增多。阑尾并没有完全展开；生发中心仍然存在于来自75岁或以上个体的5个人类样本和6岁和7岁的兔子样本中。人类的阑尾与“哺乳动物的囊等同物”有一些相同的特征；它在年轻时是一个富含B细胞的器官，卵泡和GC的形态随着年龄的增长而变化。虽然人的阑尾在许多方面与兔的阑尾和禽的滑囊相似，但其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枢淋巴器官。但也有可能外周淋巴器官共享中枢淋巴功能。对于人类阑尾和其他GALT是否也是如此，还有待进一步研究(1)。为了进一步研究人类阑尾是否作为原发性淋巴器官发挥作用，我们对3个月、4岁和9岁时采集的正常人阑尾组织的单细胞进行显微解剖，PCR扩增重排VHDHJH基因，并直接进行DNA测序。这些序列的分析正在进行中（参见Z01 AI00226-20 LI）。我们进行了单细胞微解剖液压微操作和激光捕获微解剖（LCM）的比较研究(2)，我们目前正在评估徕卡紫外激光微解剖系统（LMD）。

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 ).