title: Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria.
abstract: Secretory IgA (SIgA) directed against gut resident bacteria enables the mammalian mucosal immune system to establish homeostasis with the commensal gut microbiota after weaning. Germinal centers (GCs) in Peyer's patches (PPs) are the principal inductive sites where naive B cells specific for bacterial antigens encounter their cognate antigens and receive T-cell help driving their differentiation into IgA-producing plasma cells. We investigated the role of antigen sampling by intestinal M cells in initiating the SIgA response to gut bacteria by developing mice in which receptor activator of nuclear factor-κB ligand (RANKL)-dependent M-cell differentiation was abrogated by conditional deletion of Tnfrsf11a in the intestinal epithelium. Mice without intestinal M cells had profound delays in PP GC maturation and emergence of lamina propria IgA plasma cells, resulting in diminished levels of fecal SIgA that persisted into adulthood. We conclude that M-cell-mediated sampling of commensal bacteria is a required initial step for the efficient induction of intestinal SIgA.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rios
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Wood
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: B
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Gewirtz
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: I R
authors.initials: IR
authors.lastname: Williams
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D006706:Homeostasis; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D013559:Symbiosis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007071:Immunoglobulin A, Secretory; D053246:Receptor Activator of Nuclear Factor-kappa B