Article ID Journal Published Year Pages File Type
3354118 Immunity 2007 15 Pages PDF
Abstract

SummaryBacteria 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.

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