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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

Publication Date

13/05/2016

Volume

352

Keywords

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