Differentiation of a murine intestinal epithelial cell line (MIE) toward the M cell lineage.
M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium of Peyer's patches. These cells can transport antigens and microorganisms into underlying lymphoid tissues. Despite the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established a novel murine intestinal epithelial cell line (MIE) from the C57BL/6 mouse. MIE cells grow rapidly and have a cobblestone morphology, which is a typical feature of intestinal epithelial cells. Additionally, they express cytokeratin, villin, cell-cell junctional proteins, and alkaline phosphatase activity and can form microvilli. Their expression of Musashi-1 antigen indicates that they may be close to intestinal stem cells or transit-amplifying cells. MIE cells are able to differentiate into the M cell lineage following coculture with intestinal lymphocytes, but not with Peyer's patch lymphocytes (PPL). However, PPL costimulated with anti-CD3/CD28 MAbs caused MIE cells to display typical features of M cells, such as transcytosis activity, the disorganization of microvilli, and the expression of M cell markers. This transcytosis activity of MIE cells was not induced by T cells isolated from PPL costimulated with the same MAbs and was reduced by the depletion of the T cell population from PPL. A mixture of T cells treated with MAbs and B cells both from PPL led MIE cells to differentiate into M cells. We report here that MIE cells have the potential ability to differentiate into M cells and that this differentiation required activated T cells and B cells.
Kanaya
Takashi
T
Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku Univ., 1-1 Tsutsumidori Amamiyamachi, Aoba-ku, 981-8555 Sendai, Japan.
Miyazawa
Kohtaro
K
Takakura
Ikuro
I
Itani
Wataru
W
Watanabe
Kouichi
K
Ohwada
Shyuichi
S
Kitazawa
Haruki
H
Rose
Michael T
MT
McConochie
Huw R
HR
Okano
Hideyuki
H
Yamaguchi
Takahiro
T
Aso
Hisashi
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D018920:Coculture Techniques; D007413:Intestinal Mucosa / Q000166:cytology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008858:Microscopy, Phase-Contrast; D010581:Peyer's Patches / Q000166:cytology; D013047:Specific Pathogen-Free Organisms