Effect of mature lymphocytes and lymphotoxin on the development of the follicle-associated epithelium and M cells in mouse Peyer's patches.
OBJECTIVE
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.
Swiss Institute for Experimental Cancer Research and Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland. Nathalie.Debard@isrec.unil.ch
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N
Debard
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Sierro
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Browning
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JP
Kraehenbuhl
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000648:ultrastructure; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010581:Peyer's Patches / Q000276:immunology* / Q000648:ultrastructure; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018398:Homeodomain Proteins; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; C064658:RAG-1 protein