M cell development occurs preferentially in distal small intestinal Peyer's patches in mice lacking B cells (μMT), CCR6, or TRANCE/RANKL

Abstract

Peyer's patches (PP) are inductive sites for generation of mucosal IgA antibody responses in the small intestine (SI). M cells are specialized epithelial cells present in the follicle‐associated epithelium (FAE) of PP that acquire small particulate antigens and convey them to immune cells in the subepithelial dome. The exact molecular signals driving differentiation of FAE enterocytes into M cells have not yet been defined. In wild type (WT) mice, the extent of M cell development is equal in PP throughout the SI. B cell deficient mice (μMT) were previously shown to have smaller PP with fewer follicles and a reduced density of M cells. Whole mount immunofluorescence staining of PP from μMT mice with Ulex europaeus lectin (UEA‐1) labeled with rhodamine reveals a consistent proximal to distal gradient in the extent of M cell development with PP follicles from the proximal third of the SI containing 6.0% of the M cells in WT PP and follicles from the distal third containing 79.0% of the WT level. A proximal to distal gradient was also observed in 2 other mutant mice (CCR6 and TRANCE/RANKL knockout mice) with impaired M cell development. In TRANCE deficient mice no M cells are observed in PP from the proximal third of the SI and the number of M cells in the middle and distal third rises to just 1.9% and 12.3% of WT levels. The existence of a proximal to distal gradient in M cell development in PP from these mutant mice demonstrates that M cell development is a complex process shaped by molecular cues that differ regionally along the SI. The greater reduction in M cells in the proximal PP of the models studied may reflect the later initiation of PP organogenesis and/or the increased density of the enteric microflora in the distal SI.Supported by the NIH (DK‐64730, DK‐64399).