The development of M cells in Peyer's patches is restricted to specialized dome-associated crypts - PubMed
The development of M cells in Peyer's patches is restricted to specialized dome-associated crypts
A Gebert et al. Am J Pathol. 1999 May.
Abstract
It is controversial whether the membranous (M) cells of the Peyer's patches represent a separate cell line or develop from enterocytes under the influence of lymphocytes on the domes. To answer this question, the crypts that produce the dome epithelial cells were studied and the distribution of M cells over the domes was determined in mice. The Ulex europaeus agglutinin was used to detect M cells in mouse Peyer's patches. Confocal microscopy with lectin-gold labeling on ultrathin sections, scanning electron microscopy, and laminin immuno-histochemistry were combined to characterize the cellular composition and the structure of the dome-associated crypts and the dome epithelium. In addition, the sites of lymphocyte invasion into the dome epithelium were studied after removal of the epithelium using scanning electron microscopy. The domes of Peyer's patches were supplied with epithelial cells that derived from two types of crypt: specialized dome-associated crypts and ordinary crypts differing not only in shape, size, and cellular composition but also in the presence of M cell precursors. When epithelial cells derived from ordinary crypts entered the domes, they formed converging radial strips devoid of M cells. In contrast to the M cells, the sites where lymphocytes invaded the dome epithelium were not arranged in radial strips, but randomly distributed over the domes. M cell development is restricted to specialized dome-associated crypts. Only dome epithelial cells that derive from these specialized crypts differentiate into M cells. It is concluded that M cells represent a separate cell line that is induced in the dome-associated crypts by still unknown, probably diffusible lymphoid factors.
Figures

Crypt region neighboring the lymphoid follicles of Peyer’s patches. Semi-thin sections (a and b) show that the inner crypts that directly contact the lymphoid tissue (L) possess some morphological peculiarities. These dome-associated crypts (DAC) have a larger diameter than ordinary crypts (OC) and an oval or longish shape. The epithelium at the dome side of the dome-associated crypts is higher and more lightly stained than the epithelium opposite and contains only very few goblet cells. Immunohistochemistry for laminin (c), a regular component of basal membranes, not only outlines the two types of crypts but also detects a layer of smooth muscle cells (SM) separating the dome-associated from the ordinary crypts. Serial sections and longitudinal sections revealed that this layer is part of the lamina muscularis mucosae. Magnification, ×50 (a), × 500 (b), and ×175 (c).

Cross sections of a dome-associated crypt (a and b) and an ordinary crypt (c). The micrographs were taken from the same ultrathin section lectin-gold labeled for α1–2-linked fucose residues. In the upper third of the dome-associated crypts (a), a few epithelial cells, mostly located at the dome side of these flattened crypts, possessed thick irregular microvilli (arrows). Whereas the brush border of these M cell precursors was labeled by the lectin (b), that of the remaining epithelial cells lacked gold particles. Some mucus in the crypt lumen and in some of the goblet cells was also lectin positive. In contrast, the brush border of epithelial cells in ordinary crypts (c) remained unlabeled. UEA-I colloidal gold 20 nm; magnification, ×8600 (a) and × 17,500 (b and c).

Scanning electron microscopy of a single microdissected dome (a) of a murine Peyer’s patch. The M cells are identified by their relatively short, dark brush border; they are restricted to the dome epithelium (upper half in b, asterisks in c and e). Crypts (arrows) are opening to the cleft between the dome and the neighboring villi. Whereas the crypts shown in c and e do produce M cells and form M-cell-rich strips on the flank of the dome, no such cells are produced by the crypt shown in d. Note that the mouths of the M-cell-producing dome-associated crypts are mostly flattened (e), whereas those of ordinary crypts are typically round (d). Magnification, ×120 (a), ×1350 (b), and ×2100 (c–e).

Low-power confocal laser scanning microscopy of a microdissected Peyer’s patch dome (D) and adjacent villi (V). The Ulex europaeus agglutinin (UEA-I-TRITC) binds to the M cells which are most numerous at the flanks of the domes. In addition, brush cells and the mucus of some immature goblet cells in the crypts are labeled by the lectin. The M cells are not randomly distributed over the domes, but arranged in radial strips, rich or poor in M cells. Magnification, × 70 (a), maximal projection of 34 optical sections, and ×170 (b), maximal projection of 38 optical sections.

Confocal view of a microdissected UEA-I-TRITC-labeled dome (a) and higher magnifications (b–d, frame in a) of the top (T), the flanks, and the base with associated crypts. Maximal projections (a and b), which provide an extended depth of focus, reveal radial strips rich in M cells (white arrows) and others poor in M cells (black arrow). Single optical sections from the same image stack running across the crypt region (c and d) show that each strip is associated with an individual crypt. Most of the inner crypts are relatively large in diameter (c) and associated with M-cell-rich strips (white arrows). The M-cell-poor strips, however, are associated with smaller crypts (black arrow) that resemble ordinary crypts in size and shape (d). It must be noted that the three crypts were at different positions along the z axis and therefore are seen in different optical sections. Magnification, ×90 (a), maximal projection of 33 optical sections; ×280 (b), maximal projection of 101 optical sections; ×280 (c), section 74 of the image stack shown in b; and ×280 (d), section 86 of the image stack shown in b.

Ultrathin sections lectin-gold labeled for α1–2-linked fucose residues showing the Peyer’s patch dome epithelium of four mice. The M cells (M) are characterized by short stub-like microvilli and numerous small vesicles in their apical cytoplasm. Of 98 M cells identified as such by these morphological criteria, 95 were intensely labeled at the apical membrane and in the apical cytoplasm. In contrast, cells morphologically identified as enterocytes (E) by their typical dense brush border lacked gold particles. The arrows point to the junctional complexes between M cells and enterocytes. UEA-I colloidal gold 20 nm; magnification, ×22,000 (a–d).

Scanning electron microscopy of a murine Peyer’s patch (a) after removal of the epithelium. Whereas the basement membrane of ordinary villi and crypts shows only a few small pores, that of the domes (b) possesses numerous holes. Small roundish cells, probably representing trespassing lymphocytes, were found in or near some of these holes (c). In the corresponding images b and d, the holes of the dome epithelial basement membrane are labeled by dots. Because the periphery of the domes was slightly out of focus and/or covered with some detritus, a region of interest (ROI) was defined and analyzed. All twelve domes examined by this method showed an irregular random distribution of holes over the dome surface and in particular no radial strips rich or poor in holes. The arrows in a point to the openings of the dome-associated crypts. Magnification, ×45 (a), ×200 (b), ×560 (c), and ×200 (d).
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