title: Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma.
abstract: 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.
authors.affiliation: Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Munari
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Cangi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
authors.forename: Mario M
authors.initials: MM
authors.lastname: D'Elios
authors.forename: William
authors.initials: W
authors.lastname: Vermi
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
chemical_list: C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13