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

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.