Gut-associated Lymphoid Tissue Contains the Molecular Machinery to Support T-cell-dependent and T-cell-independent Class Switch Recombination

Mucosal Immunol. 2009 Nov;2(6):495-503. doi: 10.1038/mi.2009.106. Epub 2009 Sep 9.

Abstract

A PRoliferation-Inducing Ligand (APRIL) is a secreted cytokine member of the tumor necrosis factor family. It is a B-cell survival factor that also induces class switch recombination (CSR) toward immunoglobulin A (IgA), independent of T cells. It is therefore an important contributor to the maintenance of the mucosal immunological barrier, which has been linked to a putative extrafollicular inductive phase of the IgA response in lamina propria. By immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) on microdissected tissue from normal human gut, we observed APRIL expression, together with TACI (transmembrane activator and CAML interactor) and BCMA (B-cell maturation antigen), in gut-associated lymphoid tissue (GALT), lamina propria, and in the epithelium of stomach, small and large intestine, and rectum. However, no activation-induced cytidine deaminase (AID) expression (an absolute requirement for class switching) was detected in lamina propria by IHC or qRT-PCR. APRIL and its receptors were only observed alongside AID in GALT, showing that GALT contains the apparatus to support both T-independent and T-dependent routes to IgA CSR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Cell Maturation Antigen / biosynthesis
  • B-Cell Maturation Antigen / immunology
  • Cytidine Deaminase / biosynthesis
  • Cytidine Deaminase / immunology
  • Gastric Mucosa / immunology*
  • Gastric Mucosa / metabolism
  • Humans
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A / immunology
  • Immunoglobulin Class Switching / immunology*
  • Immunohistochemistry
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Microdissection
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • Transmembrane Activator and CAML Interactor Protein / biosynthesis
  • Transmembrane Activator and CAML Interactor Protein / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / biosynthesis
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology

Substances

  • B-Cell Maturation Antigen
  • Immunoglobulin A
  • TNFRSF13B protein, human
  • TNFRSF17 protein, human
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase