title: IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches.
abstract: Immunoglobulin A (IgA) induction primarily occurs in intestinal Peyer's patches (PPs). However, the cellular interactions necessary for IgA class switching are poorly defined. Here we show that in mice, activated B cells use the chemokine receptor CCR6 to access the subepithelial dome (SED) of PPs. There, B cells undergo prolonged interactions with SED dendritic cells (DCs). PP IgA class switching requires innate lymphoid cells, which promote lymphotoxin-β receptor (LTβR)-dependent maintenance of DCs. PP DCs augment IgA production by integrin αvβ8-mediated activation of transforming growth factor-β (TGFβ). In mice where B cells cannot access the SED, IgA responses against oral antigen and gut commensals are impaired. These studies establish the PP SED as a niche supporting DC-B cell interactions needed for TGFβ activation and induction of mucosal IgA responses.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. andrea.reboldi@ucsf.edu jason.cyster@ucsf.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Reboldi
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Rodda
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.
authors.forename: Amha
authors.initials: A
authors.lastname: Atakilit
authors.affiliation: Lung Biology Center, Department of Medicine, University of California San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. andrea.reboldi@ucsf.edu jason.cyster@ucsf.edu.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis* / Q000235:genetics; D017578:Immunoglobulin Class Switching; D016023:Integrins / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010581:Peyer's Patches / Q000276:immunology*; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology*
chemical_list: C498126:CCR6 protein, mouse; D007071:Immunoglobulin A, Secretory; D016023:Integrins; D053259:Lymphotoxin beta Receptor; D054399:Receptors, CCR6; C403414:integrin alphavbeta8