Role Of Appendix and GALT In Development Of The Primary

我们对兔子的研究表明，幼阑尾是产生保护性抗体的细胞发育的重要部位。家兔阑尾的功能与鸟类腔上囊相似。在幼兔中，阑尾中B淋巴细胞快速生长和扩增，并发生阳性和阴性选择事件。我们相信，在阑尾选择中存活下来的细胞在外周淋巴系统中播种，并进行自我更新以维持初级库。兔的数据引导我们研究人阑尾和GALT在人免疫库和粘膜免疫发育中的作用。我们比较了正常人阑尾生发中心（GC）和不同年龄兔阑尾GC的发育。在人类和兔子的阑尾中，我们发现淋巴滤泡在出生时刚刚开始形成。在人类中大约1个月和在兔阑尾中1周时，Germination中心变得明显。大多数淋巴发育发生在人类的第一年内，兔阑尾的前12周内。人和兔阑尾的类阑尾组织在成年期开始萎缩。滤泡变小、数量减少，结缔组织和平滑肌增多。阑尾没有完全内卷;在5个75岁或以上的人样本和6岁和7岁的兔子样本中仍然存在生发中心。人类阑尾具有“哺乳动物囊等同物”的某些特征;在年轻时，阑尾是一个富含B细胞的器官，卵泡和GC的形态随年龄而变化。虽然人类阑尾在许多方面与兔阑尾和禽法氏囊相似，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，外周淋巴器官也可能共享某些中枢淋巴功能。这是否适用于人类阑尾和其他GALT需要进一步研究（1）。为了进一步研究人类阑尾是否作为初级淋巴器官发挥作用，我们从3个月、4岁和9岁的正常人阑尾组织中显微解剖单个细胞，进行重排的VHDHJH基因的PCR扩增和直接DNA测序。这些序列的分析正在进行中（另见Z 01 AI 00226 -20 LI）。我们对液压显微操作和激光捕获显微切割（LCM）进行了单细胞显微切割的比较研究（2），我们目前正在评估Leica UV激光显微切割系统（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 ).