Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI

Nat Immunol. 2007 Mar;8(3):294-303. doi: 10.1038/ni1434. Epub 2007 Jan 28.

Abstract

Epithelial cells (ECs) transport class-switched immunoglobulin G (IgG) and IgA antibodies across mucous membranes. Whether ECs initiate class switching remains unknown. Here we found that ECs lining tonsillar crypts formed pockets populated by B cells expressing activation-induced cytidine deaminase (AID), an enzyme associated with ongoing class switching. ECs released B cell-activating AID-inducing factors after sensing microbial products through Toll-like receptors. The resulting class switching was amplified by thymic stromal lymphopoietin, an epithelial interleukin 7-like cytokine that enhanced the B cell 'licensing' function of dendritic cells, and was restrained by secretory leukocyte protease inhibitor, an epithelial homeostatic protein that inhibited AID induction in B cells. Thus, ECs may function as mucosal 'guardians' orchestrating frontline IgG and IgA class switching through a Toll-like receptor-inducible signaling program regulated by secretory leukocyte protease inhibitor.NOTE: In the version of this article initially published online, the middle label above Figure 6c is incorrect. The correct label should be 'BAFF'. The error has been corrected for all versions of the article.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Flow Cytometry
  • Humans
  • Immunity, Mucosal
  • Immunoblotting
  • Immunoglobulin A / immunology
  • Immunoglobulin Class Switching*
  • Immunoglobulin G / immunology
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • RNA, Viral / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Secretory Leukocyte Peptidase Inhibitor / immunology*
  • Secretory Leukocyte Peptidase Inhibitor / metabolism
  • Signal Transduction / immunology*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism

Substances

  • B-Cell Activating Factor
  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin G
  • RNA, Viral
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • TNFSF13B protein, human
  • Toll-Like Receptors
  • Interleukin-10
  • thymic stromal lymphopoietin