Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL

Immunity. 2007 Jun;26(6):812-26. doi: 10.1016/j.immuni.2007.04.014.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / microbiology
  • Bacteria / immunology*
  • Bacterial Vaccines / immunology
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / analysis
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Humans
  • Immunoglobulin A / genetics*
  • Immunoglobulin Class Switching*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Intestines / cytology
  • Intestines / immunology
  • Intestines / microbiology
  • Molecular Sequence Data
  • Mucous Membrane / immunology
  • Toll-Like Receptors / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism*


  • Bacterial Vaccines
  • CD40 Antigens
  • Cytokines
  • Immunoglobulin A
  • Tnfsf13 protein, mouse
  • Toll-Like Receptors
  • Tumor Necrosis Factor Ligand Superfamily Member 13