Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI Academic Article uri icon

Overview

MeSH Major

  • B-Lymphocytes
  • Epithelial Cells
  • Immunoglobulin Class Switching
  • Secretory Leukocyte Peptidase Inhibitor
  • Signal Transduction

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 date

  • March 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/ni1434

PubMed ID

  • 17259987

Additional Document Info

start page

  • 294

end page

  • 303

volume

  • 8

number

  • 3