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

我们在兔子身上的研究表明，年轻的 阑尾是细胞发育的重要部位 产生保护性抗体。兔阑尾有功能 与Fabricius的禽法氏囊相似。在幼兔体内， B淋巴细胞的快速生长和扩增。 附录，以及肯定和否定选择事件发生。我们 相信在阑尾种子中幸存下来的细胞 外周淋巴系统并经历自我更新以维持 主要的曲目。关于兔子的数据让我们发起了一项 人的阑尾和GALT在急性胰腺炎中的作用评价 人类免疫谱系和粘膜的研究进展 豁免权。我们从询问淋巴细胞发育的年龄开始 最明显的是在人类的阑尾。我们的结论是 根据对8-18个样本的初步检查结果 各种各样的污渍。石蜡苏木精伊红染色 首先用正常人的阑尾切片检查 生发中心(GC)的发育阶段。仅限4天 可见初级卵泡。淋巴滤泡似乎 在生命的第一年内迅速发育，并被维持或 在童年时期，在大小和数量上逐渐增加。淋巴组织 一个8个月大婴儿的阑尾组织发育 就像一个10岁的孩子一样。在4岁时的样本中 几个月到16年，GC明显，光线清晰， 暗区。样本中的淋巴滤泡已经开始萎缩。 从一个16岁的孩子开始。在一个样本中没有明显的卵泡 一名25岁的男子。看起来卵泡开始变小， 青少年时期的数字。轴承细胞的分布 对不同年龄段的常见B和T细胞标志物进行了调查 石蜡切片对IgM、IgD和IgA阳性B细胞的染色 浆细胞和CD4和CD8阳性T细胞。在样本中 一个4天大的婴儿，浆细胞(PC)缺失，抗IgM 大多数滤泡细胞染色，而抗IgD染色的细胞 卵泡内不规则和抗-IgA均未染色。免疫球蛋白染色 从4个月到16年的样本中的模式相似：GC 为IgM+，外套带为IGD+，GC光区为 弱IgA+。CD_4~+和CD_8~+细胞主要分布在T细胞 与GC相邻的细胞区域。CD4+和CD8+细胞数量 同一捐赠者的GC之间差异很大，尽管T细胞 在被检查的最早年龄的卵泡中被发现。进行GC 人类阑尾的部分经历了 兔的阑尾，暗示着从一个 初级到次级淋巴器官？B细胞的分布 出现表达IgM、IgD、IgA和携带CD4的T细胞 只要GC存在，在整个开发过程中都是类似的。它是 不确定这是否适用于CD8+细胞。双重染色 对于可能的双阳性细胞是必要的，并且正在进行中。 我们在发育中生发中心发现的CD4T细胞 人类的阑尾提示它可能起到继发性的作用。 淋巴器官，但不排除它也可能 发挥主要淋巴器官的作用。人的阑尾 具有“哺乳动物法氏囊等效物”的某些特征； 其卵泡的形态和GC渐开线与 年龄(Dasso等人，1998年和正在筹备中的MS)。

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 have led us to initiate an evaluation of the role of human appendix and GALT in development of the human immune repertoire and mucosal immunity. We started by asking at what age lymphoid development is most pronounced in the human appendix. Our conclusions are based on preliminary results of examinations 8-18 specimens by various stainings. Hematoxylin and eosin staining of paraffin sections of normal human appendix was first used to examine stages of germinal center (GC) development. At 4 days, only primary follicles were found. Lymphoid follicles appeared to develop rapidly within the first year of life and be maintained or gradually increased in size and number during childhood. Lymphoid development in appendix tissue from an 8 month old child resembled that from a 10 year old. In the samples from ages 4 months to 16 years, GC were evident with clearly defined light and dark zones. Lymphoid follicles had begun to atrophy in the sample from a 16 year old. No follicles were evident in one specimen from a 25-year-old. It appears that follicles begin to diminish in size and number during the teen years. The distribution of cells bearing common B and T cell markers at various ages was investigated by staining paraffin sections for IgM, IgD and IgA positive B cells and plasma cells and for CD4 and CD8 positive T cells. In a sample from a 4-day-old child, plasma cells (PC) were absent, anti-IgM stained most follicular cells whereas anti-IgD stained cells irregularly within the follicle and anti-IgA did not stain. Ig staining patterns were similar in the samples from 4 months to 16 years: GC were IgM+, mantle zones were IgD+, and GC light zones were weakly IgA+. CD4+ and CD8+ cells were found mainly in the T cell areas bordering the GC. Numbers of CD4+ and CD8+ cells varied greatly between GC from the same donor although T cells were found in the follicles from the earliest age examined. Do GC of the human appendix undergo the developmental changes seen in the rabbit appendix which are suggestive of transformation from a primary to secondary lymphoid organ? The distributions of B cells expressing IgM, IgD and IgA, and of T cells bearing CD4 appear similar throughout development as long as GC are present. It is uncertain whether this holds true for CD8+ cells. Double staining for possible double-positive cells is necessary and is in progress. Our finding of CD4 T cells in the germinal centers of developing human appendix suggests that it may function as a secondary lymphoid organ but does not exclude the possibility that it may also play a role as a primary lymphoid organ. The human appendix shares some characteristics of a "mammalian bursa equivalent"; the morphology of its follicles and the fact that the GC involute with age (Dasso et al., 1998 and ms in preparation).