Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a pre-neoplastic 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 upon 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.

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

CASSATELLA, Marco Antonio;
2011-01-01

Abstract

Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a pre-neoplastic 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 upon 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.
2011
Tumor-associated macrophages; gastric MALT lymphoma; Immunobiology
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/351905
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