Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL

• DOI: 10.1016/j.immuni.2007.04.014
• Publication Date: 2007-06-22T11:22:49Z
• Authors: Bing He; Weifeng Xu; Paul A. Santini; Alexandros D. Pol...; April Chiu; Jeannelyn Estrella; Meimei Shan; Amy Chadburn; Vincenzo Villanacci; Alessandro Plebani; Daniel M. Knowles; Maria Rescigno; Andrea Cerutti
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Immunology; Molecular Sequence Data; Tumor Necrosis Factor Ligand Superfamily Member 13; 03 medical and health sciences; Immunology and Allergy; Humans; CD40 Antigens; Intestinal Mucosa; MOLIMMUNO; B-Lymphocytes; Mucous Membrane; Bacteria; Base Sequence; Toll-Like Receptors; Dendritic Cells; Immunoglobulin Class Switching; IGA-producing cells; gut lamina propria; naive B-cells; dendritic cells; somatic hypermutation; commensal bacteria; DNA recombination; differentiation; homeostasis; activation; Immunoglobulin A; 3. Good health; Intestines; Infectious Diseases; CELLIMMUNO; Bacterial Vaccines; Cytokines

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.