Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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

Pages

aaf4822 - aaf4822

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