Title | Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, Shan M, Chadburn A, Villanacci V, Plebani A, Knowles DM, Rescigno M, Cerutti A |
Journal | Immunity |
Volume | 26 |
Issue | 6 |
Pagination | 812-26 |
Date Published | 2007 Jun |
ISSN | 1074-7613 |
Keywords | B-Lymphocytes, Bacteria, Bacterial Vaccines, Base Sequence, CD4-Positive T-Lymphocytes, CD40 Antigens, Cytokines, Dendritic Cells, Humans, Immunoglobulin A, Immunoglobulin Class Switching, Intestinal Mucosa, Intestines, Molecular Sequence Data, Mucous Membrane, Toll-Like Receptors, Tumor Necrosis Factor Ligand Superfamily Member 13 |
Abstract | Bacteria colonize the intestine shortly after birth and thereafter exert several beneficial functions, including induction of protective immunoglobulin A (IgA) antibodies. The distal intestine contains IgA(2), which is more resistant to bacterial proteases than is IgA(1). The mechanism by which B cells switch from IgM to IgA(2) remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA(2) class switching in B cells, including IgA(1)-expressing B cells arriving from mucosal follicles, through a CD4(+) T cell-independent pathway involving a proliferation-inducing ligand (APRIL). IECs released APRIL after sensing bacteria through Toll-like receptors (TLRs) and further increased APRIL production by activating dendritic cells via thymic stromal lymphopoietin. Our data indicate that bacteria elicit IgA(2) class switching by linking lamina propria B cells with IECs through a TLR-inducible signaling program requiring APRIL. Thus, mucosal vaccines should activate IECs to induce more effective IgA(2) responses. |
DOI | 10.1016/j.immuni.2007.04.014 |
Alternate Journal | Immunity |
PubMed ID | 17570691 |
Grant List | T32 AI07621 / AI / NIAID NIH HHS / United States R21 AI057130 / AI / NIAID NIH HHS / United States R01 AI057653 / AI / NIAID NIH HHS / United States AI057653 / AI / NIAID NIH HHS / United States R01 AI074378 / AI / NIAID NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.