Effect of mature lymphocytes and lymphotoxin on the development of the follicle-associated epithelium and M cells in mouse Peyer's patches

Gastroenterology. 2001 Apr;120(5):1173-82. doi: 10.1053/gast.2001.22476.


Background and aims: Mechanisms regulating M-cell formation are still poorly understood. In vitro studies showed that lymphocytes trigger the conversion of enterocyte cell lines into M cell-like cells on coculture, whereas in vivo their role in M cell differentiation is still elusive. Our aim was first to examine Rag-1-/- mice, lacking B and T lymphocytes, for the presence of intestinal M cells. Second, we investigated the role of lymphotoxin alphabeta signaling on M-cell formation, given its pivotal role in the development of mouse Peyer's patches.

Methods: Small intestines of Rag-1-/- mice, injected or not with soluble lymphotoxin beta receptor-immunoglobulin fusion protein, were analyzed morphologically using whole mount cytochemical staining, immunohistochemistry, and electron microscopy.

Results: Small Peyer's patch-like aggregates were found in Rag-1-/- mice in normal number and location. The overlying epithelium of such aggregates was reduced in size but still harbored M cells. In vivo neutralization of lymphotoxin beta-receptor signaling partially reduced the percentage of M cells.

Conclusions: The absence of mature lymphocytes does not prevent the formation of M cells, indicating that the signaling molecules that support M-cell differentiation, such as lymphotoxin alphabeta, may also be supplied by non-B and non-T cells. Mature B lymphocytes, however, are required for the formation of a full-sized follicle-associated epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Female
  • Homeodomain Proteins / genetics
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / ultrastructure
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Microscopy, Electron
  • Microscopy, Electron, Scanning
  • Peyer's Patches / immunology*
  • Peyer's Patches / ultrastructure
  • Receptors, Tumor Necrosis Factor / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*


  • Homeodomain Proteins
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Receptors, Tumor Necrosis Factor
  • RAG-1 protein