TY - JOUR
T1 - Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL
AU - He, Bing
AU - Xu, Weifeng
AU - Santini, Paul A.
AU - Polydorides, Alexandros D.
AU - Chiu, April
AU - Estrella, Jeannelyn
AU - Shan, Meimei
AU - Chadburn, Amy
AU - Villanacci, Vincenzo
AU - Plebani, Alessandro
AU - Knowles, Daniel M.
AU - Rescigno, Maria
AU - Cerutti, Andrea
PY - 2007/6/22
Y1 - 2007/6/22
N2 - 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.
AB - 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.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=34250205694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250205694&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2007.04.014
DO - 10.1016/j.immuni.2007.04.014
M3 - Article
C2 - 17570691
AN - SCOPUS:34250205694
VL - 26
SP - 812
EP - 826
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -