Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma

Blood. 2011 Jun 16;117(24):6612-6. doi: 10.1182/blood-2010-06-293266. Epub 2011 Apr 28.


Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a preneoplastic condition of the mucosa associated lymphoid tissue (MALT), which may evolve to a B-cell lymphoma. While it is well established that the initial neoplastic proliferation of B cells is antigen-driven and dependent on the helper activity of HP-specific T cells, it needs to be elucidated which cytokine or soluble factor(s) promote B-cell activation and lymphomagenesis. Herein, we originally report that gastric MALT lymphoma express high levels of a proliferation inducing ligand (APRIL), a novel cytokine crucial in sustaining B-cell proliferation. By immunohistochemistry, we demonstrate that APRIL is produced almost exclusively by gastric lymphoma-infiltrating macrophages located in close proximity to neoplastic B cells. We also show that macrophages produce APRIL on direct stimulation with both HP and HP-specific T cells. Collectively, our results represent the first evidence for an involvement of APRIL in gastric MALT lymphoma development in HP-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cells, Cultured
  • Chronic Disease
  • Gastric Mucosa / immunology
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Gastritis / immunology
  • Gastritis / metabolism
  • Gastritis / pathology
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / complications
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / physiology
  • Humans
  • Lymphoma, B-Cell, Marginal Zone / etiology
  • Lymphoma, B-Cell, Marginal Zone / metabolism*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Precancerous Conditions / immunology
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism*


  • TNFSF13 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13