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

Journal article

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 avb8-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: Reboldi, A; Arnon, T; Rodda, L; Atakilit, A; Sheppard, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science
• Volume: 352
• Issue: 6287
• Pages: aaf4822
• Publication date: 2016-05-13
• Acceptance date: 2016-03-30
• DOI: 10.1126/science.aaf4822
• ISSN: 1095-9203, 0036-8075
• Language: English
• Keywords: mice; lymphotoxin beta receptor; animals; integrins; immunoglobulin class switching; receptors, CCR6; peyer's patches; b-lymphocytes; intestinal mucosa; cell movement; mice, mutant strains; dendritic cells; cell communication; lymphocyte activation; SBTMR; immunoglobulin a, secretory