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

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...

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Bibliographic Details
Published in:Blood Vol. 117; no. 24; p. 6612
Main Authors: Munari, Fabio, Lonardi, Silvia, Cassatella, Marco A, Doglioni, Claudio, Cangi, Maria Giulia, Amedei, Amedeo, Facchetti, Fabio, Eishi, Yoshinobu, Rugge, Massimo, Fassan, Matteo, de Bernard, Marina, D'Elios, Mario M, Vermi, William
Format: Journal Article
Language:English
Published: United States 16.06.2011
Subjects:
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
ISSN:1528-0020, 1528-0020
Online Access:Get more information
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Summary: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.
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ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2010-06-293266