Absence of Antigen-Sampling M Cells Compromises Both the Antigen-Specific and Nonspecific Components of the Secretory IgA Response to Monocolonization of Mice with SFB

The gut mucosal immune system produces abundant secretory IgA that assists in establishing homeostasis with the commensal microbiota. Much of this IgA response is triggered by the microbiota, although the precise cellular pathways associated with responses to individual bacterial species remain to be characterized. Using a conditional RANK knockout mouse lacking intestinal M cells in Peyer’s patches (RANKΔIEC strain), we previously demonstrated that M cells play a key role in efficient initiation of the overall IgA response to commensal microbiota. To further our understanding of the role that M cells play in generation of IgA responses to specific bacterial species, we studied the kinetics of fecal IgA responses in RANKΔIEC mice that were germ-free or monocolonized with segmented filamentous bacteria (SFB). Under germ-free conditions wild-type and RANKΔIEC mice produced equivalent low amounts of secretory IgA, indicating that the low level of production of natural IgA and IgA directed against non-microbiota environmental antigens does not depend on M cells. Since SFB are known to be robust inducers of both secretory IgA and Th17 responses, we also assessed the contribution of M cells to fecal IgA responses occurring in mice monocolonized with SFB. Both the rapid nonspecific total IgA response detected by ELISA and the more gradual specific anti-SFB IgA response assessed by bacterial flow cytometry were depressed, but not ablated, in M-cell deficient mice. Our results indicate that M cells are critical, nonredundant mediators of intestinal antigen sampling required for efficient development of mucosal IgA to antigens associated with the commensal microbiota.