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Compartmentalization of Peyer’s Patch Anlagen Before Lymphocyte Entry¹

Hiroyuki Hashi^2,*,, Hisahiro Yoshida^*, Kenya Honda^*, Stuart Fraser^*, Hajime Kubo, Masaaki Awane, Arimichi Takabayashi, Hideki Nakano, Yoshio Yamaoka and Shin-Ichi Nishikawa^*

Departments of ^* Molecular Genetics and Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and Division of Cardiology, Duke University Medical Center, Durham, NC 27710

We have shown that Peyer’s patch (PP) first develops as a simple and even cell aggregation during embryogenesis. To investigate when and how such a simple cell aggregation forms the complex PP architecture, we analyzed the distribution of cells expressing IL-7R (PP inducer cells), VCAM-1 (mesenchymal cells), CD11c (dendritic cells), and mature lymphocytes by whole-mount immunostaining of 17.5 days postcoitus to 2 days postpartum mouse gut. Our results show that compartmentalization of PP anlagen commences at day 18.5 of gestation by clustering and subsequent follicle formation of IL-7R⁺, VCAM-1⁺, and CD11c⁺ cells. This process adds the primitive architecture of PP anlage with several follicles in which IL-7R⁺ cells localize in the center, while VCAM-1⁺ and CD11c⁺ cells localize at the fringe. This follicle formation is accompanied by the establishment of PP-specific vascular network expressing mucosal addressin cellular adhesion molecule-1. Mature B and T lymphocytes entering in the PP anlage are distributed promptly to their own target zones; B cells to the follicle and T cells to nonfollicular zones. Our analysis of scid/scid mouse indicate that the initial processes including formation of PP-specific vascular network occur in the absence of lymphocytes. These observations indicate that the basic architecture of PP is formed by a set of cell lineages assembled during the initial phase of induction of PP anlagen before entry of mature lymphocytes.

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