Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL
CD4-Positive T-Lymphocytes
0301 basic medicine
Immunology
Molecular Sequence Data
Tumor Necrosis Factor Ligand Superfamily Member 13
03 medical and health sciences
Immunology and Allergy
Humans
CD40 Antigens
Intestinal Mucosa
MOLIMMUNO
B-Lymphocytes
Mucous Membrane
Bacteria
Base Sequence
Toll-Like Receptors
Dendritic Cells
Immunoglobulin Class Switching
IGA-producing cells; gut lamina propria; naive B-cells; dendritic cells; somatic hypermutation; commensal bacteria; DNA recombination; differentiation; homeostasis; activation
Immunoglobulin A
3. Good health
Intestines
Infectious Diseases
CELLIMMUNO
Bacterial Vaccines
Cytokines
DOI:
10.1016/j.immuni.2007.04.014
Publication Date:
2007-06-22T11:22:49Z
AUTHORS (13)
ABSTRACT
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.
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