IgA Production Requires B Cell Interaction with Subepithelial Dendritic Cells in Peyer’s Patches

Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG.

Image of Lauren Rodda and Jason Cyster

Lauren Rodda (left) and Jason Cyster (right)

Photo of Andrea Reboldi

Andrea Reboldi

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) as revealed by intravital microscopy. 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.

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