title: Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL.
abstract: Bacteria colonize the intestine shortly after birth and thereafter exert several beneficial functions, including induction of protective immunoglobulin A (IgA) antibodies. The distal intestine contains IgA(2), which is more resistant to bacterial proteases than is IgA(1). The mechanism by which B cells switch from IgM to IgA(2) remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA(2) class switching in B cells, including IgA(1)-expressing B cells arriving from mucosal follicles, through a CD4(+) T cell-independent pathway involving a proliferation-inducing ligand (APRIL). IECs released APRIL after sensing bacteria through Toll-like receptors (TLRs) and further increased APRIL production by activating dendritic cells via thymic stromal lymphopoietin. Our data indicate that bacteria elicit IgA(2) class switching by linking lamina propria B cells with IECs through a TLR-inducible signaling program requiring APRIL. Thus, mucosal vaccines should activate IECs to induce more effective IgA(2) responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Santini
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Polydorides
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Jeannelyn
authors.initials: J
authors.lastname: Estrella
authors.forename: Meimei
authors.initials: M
authors.lastname: Shan
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D001419:Bacteria / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007422:Intestines / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
chemical_list: D001428:Bacterial Vaccines; D019013:CD40 Antigens; D016207:Cytokines; D007070:Immunoglobulin A; C491959:Tnfsf13 protein, mouse; D051193:Toll-Like Receptors; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13