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 IgA2, which is more resistant to bacterial proteases than is IgA1. The mechanism by which B cells switch from IgM to IgA2 remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA2 class switching in B cells, including IgA1-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 IgA2 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 IgA2 responses.
Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL / B. He, W. Xu, P.A. Santini, A.D. Polydorides, A. Chiu, J. Estrella, M. Shan, A. Chadburn, V. Villanacci, A. Plebani, D.M. Knowles, M. Rescigno, A. Cerutti. - In: IMMUNITY. - ISSN 1074-7613. - 26:6(2007), pp. 812-826.
Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL
M. RescignoPenultimo
;
2007
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 IgA2, which is more resistant to bacterial proteases than is IgA1. The mechanism by which B cells switch from IgM to IgA2 remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA2 class switching in B cells, including IgA1-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 IgA2 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 IgA2 responses.File | Dimensione | Formato | |
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