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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.

Original publication

DOI

10.1126/science.aaf4822

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

05/2016

Volume

352

Addresses

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.

Keywords

Intestinal Mucosa, Peyer's Patches, B-Lymphocytes, Dendritic Cells, Animals, Mice, Mice, Mutant Strains, Immunoglobulin A, Secretory, Integrins, Lymphocyte Activation, Cell Communication, Cell Movement, Immunoglobulin Class Switching, Lymphotoxin beta Receptor, Receptors, CCR6