IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches

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-beta receptor (LT beta R)-dependent maintenance of DCs. PP DCs augment IgA production by integrin alpha nu beta 8-mediated activation of transforming growth factor-beta (TGF beta). 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 TGF beta activation and induction of mucosal IgA responses.