Three distinctive steps in Peyer's patch formation of murine embryo

Three distinctive steps in Peyer's patch formation of murine embryo
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DOI:
10.1093/intimm/9.4.507
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发表时间:
1997-04-01
影响因子:
4.4
通讯作者:
Nishikawa, S
Nishikawa, S
中科院分区:
医学3区
文献类型:
--
作者:
Adachi, S;Yoshida, H;Nishikawa, S

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Peyer氏斑(PP)形成过程的研究由于难以确定其在胚胎中的初始步骤而受到阻碍。在这项研究中,我们克服了这个问题,通过使用针对PP发育部位积累的细胞中表达的分子的mAb进行整体免疫组化。这种方法灵敏到足以区分发育中的胃肠道中的微小细胞团,我们分析了各种表面标志表达的时间进程,发现PP的形成经历了三个连续的步骤。第一个是在性交后15.5天出现VCAM-1(+)细胞团。对VCAM-1(+)簇的组织学检查表明,VCAM-1(+)细胞代表基质成分。第二步的特征是在17.5DP.C.时,表达Ia、IL-7R或CD4的圆形细胞聚集。仅在18.5DP.C.开始的最后一步才检测到表达CD3或B220的淋巴细胞。使用这些标记中的任何一个,最初在空肠上部检测到聚集,并随着簇数的增加而扩展到结肠。在新生儿阶段,无论用于检测的抗体是什么,这个数字都达到了8到9个。在Aly/Aly突变小鼠中,成年小鼠没有发现淋巴结或PP,这三个步骤都没有检测到。另一方面,在成熟淋巴细胞形成缺陷的SCID小鼠中,第一步和第二步继续进行,而第三步未被检测到。这些发现表明,每一步的进展确实受到不同机制的调控。
Investigation of the process of Peyer's patch (PP) formation has been hampered by difficulties in identifying its initial step in the embryo. In this study, we overcame this problem by means of whole-mount immunohistochemistry using mAb against the molecules which were expressed in the cells accumulated at the site of PP development. This method was sensitive enough to distinguish a minute cell cluster in the developing gastrointestinal tract, We analyzed the time course of the expression of various surface markers and found that PP formation proceeds through three successive steps. The first is the appearance of a VCAM-1(+) cell cluster at 15.5 days postcoitus (d.p.c.). Histological examination of the VCAM-1(+) clusters suggested that VCAM-1(+) cells represent a stromal component. The second step is characterized by the accumulation of round cells expressing Ia, IL-7R or CD4 at 17.5 d.p.c. Lymphocytes expressing CD3 or B220 were detected only in the final step which started at 18.5 d.p.c. Using any of these markers, the aggregation was initially detected on the upper jejunum and it extended to the colon as the number of clusters increased. At the neonatal stage, the number reached up to eight or nine, irrespective of the antibodies used for the detection. In the aly/aly mutant mouse, where no lymph nodes or PP are found in the adult, none of these three steps was detected. On the other hand, in the SCID mouse that is defective in the formation of mature lymphocytes, the first and second step proceeded, whereas the third step was undetectable. These findings suggest that the progression of each step is indeed regulated by different mechanisms.