Intestinal bacteria trigger T cell-independent immunoglobulin A(2) 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 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.
He
Bing
B
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Xu
Weifeng
W
Santini
Paul A
PA
Polydorides
Alexandros D
AD
Chiu
April
A
Estrella
Jeannelyn
J
Shan
Meimei
M
Chadburn
Amy
A
Villanacci
Vincenzo
V
Plebani
Alessandro
A
Knowles
Daniel M
DM
Rescigno
Maria
M
Cerutti
Andrea
A
D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D001419:Bacteria / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007422:Intestines / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
D001428:Bacterial Vaccines; D019013:CD40 Antigens; D016207:Cytokines; D007070:Immunoglobulin A; C491959:Tnfsf13 protein, mouse; D051193:Toll-Like Receptors; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13