We have shown that Fever's patch (PP) first develops as a simple and even c
ell aggregation during embryogenesis. To investigate when and how such a si
mple cell aggregation forms the complex PP architecture, we analyzed the di
stribution of cells expressing IL-7R alpha (PP inducer cells), VCAM-1 (mese
nchymal cells), CD11c (dendritic cells), and mature lymphocytes by whole-mo
unt immunostaining of 17.5 days postcoitus to 2 days postpartum mouse gut,
Our results show that compartmentalization of PP anlagen commences at day 1
8.5 of gestation by clustering and subsequent follicle formation of IL-7R a
lpha (+), VCAM-1(+), and CD11c(+) cells, This process adds the primitive ar
chitecture of PP anlage with several follicles in which IL-7R alpha (+) cel
ls localize in the center, while VCAM-1(+) and CD11c(+) cells localize at t
he fringe, This follicle formation is accompanied by the establishment of F
P-specific vascular network expressing mucosal addressin cellular adhesion
molecule-1. Mature B and T lymphocytes entering in the PP anlage are distri
buted promptly to their own target zones; B cells to the follicle and T cel
ls to nonfollicular zones. Our analysis of scid/scid mouse indicate that th
e initial processes including formation of PP-specific vascular network occ
ur in the absence of lymphocytes. These observations indicate th at the bas
ic 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 lymphoc
ytes.