Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL

Bing He, Weifeng Xu, Paul A. Santini, Alexandros D. Polydorides, April Chiu, Jeannelyn Estrella, Meimei Shan, Amy Chadburn, Vincenzo Villanacci, Alessandro Plebani, Daniel M. Knowles, Maria Rescigno, Andrea Cerutti

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)812-826
Number of pages15
JournalImmunity
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 22 2007

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    He, B., Xu, W., Santini, P. A., Polydorides, A. D., Chiu, A., Estrella, J., Shan, M., Chadburn, A., Villanacci, V., Plebani, A., Knowles, D. M., Rescigno, M., & Cerutti, A. (2007). Intestinal Bacteria Trigger T Cell-Independent Immunoglobulin A2 Class Switching by Inducing Epithelial-Cell Secretion of the Cytokine APRIL. Immunity, 26(6), 812-826. https://doi.org/10.1016/j.immuni.2007.04.014