Development of Peyer's patches, follicle-associated epithelium and M cell: Lessons from immunodeficient and knockout mice

Abstract

Studies with immunodeficient and knockout mice have re- vealed that the development of mucosa-associated lymphoid tissues (MALT) and peripheral lymphoid nodes share com- mon mechanisms, but also require distinct signals. Gene disruption of lymphotoxins or their cognate receptors affects both Peyer's patch and lymph node organogenesis. Disrup- tion of the osteoprotegerin TNF-family member gene does not impair Peyer's patch development, but prevents formation of peripheral lymph nodes. Peyer's patch do not form in mice with a deleted gene encoding a B lymphocyte-specific chemokine receptor, while most peripheral lymph nodes, ex- cept inguinal, are normal in numbers and architecture. In B or T lymphocyte-deficient mice, Peyer's patches, with their overlying follicle-associated epithelium (FAE), are present although reduced in number and size. No Peyer's patches develop in RAG deficient mice. Formation of FAE with typical M cells has not been analyzed in these mice. M cell formation requires the close association of immune cells with differentiated enterocytes and their conversion appears to be transcriptionally regulated. The development of MALT, FAE and probably M cells is a multistep process that requires signalling pathways common to all secondary lymphoid tissues, but also MALT-specific factors.