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

Background & 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 alpha beta 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 P-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 alpha beta, 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.