The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma

Abstract

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue

“…H. pylori infection causes increasingly severe gastric mucosal damage, and the development and progression of gastric MALT lymphomas caused by H. pylori infection are also progressive. This is especially so in gastritis associated with H. pylori infection, where the gastric mucosa has a large amount of lymphoid hyperplasia, including the reactive hyperplasia of lymphoid follicles [5,19,20].…”

“…Epidemiologic and laboratory studies have found that Helicobacter pylori (H. pylori ) is the most common pathogen that infects the gastric mucosa, and the development of gastric MALT lymphoma is closely related to H. pylori infection [5,6]. It is reported that 80% of early gastric MALT lymphomas can regress after the elimination of H. pylori , and in addition to treatment to eliminate H. pylori, surgery, chemotherapy, radiotherapy, or a combination of these methods are treatment choices [7,8].…”

Increased IL-17A Serum Levels and Gastric Th17 Cells in Helicobacter pylori-Infected Patients with Gastric Premalignant Lesions

“…The mitogenic index (MI) was determined as the ratio between mean values of CPM obtained in stimulated cultures and those obtained in unstimulated ones (medium alone). Mitogenic index >5 was considered as positive [ 45 ].…”

Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer

“…H. pylori infection increased the incidence of low-grade gastric MALT lymphoma by an odds ratio of 2.8 times compared with H. pylori -negative individuals ( 105 ). Within gastric MALT lymphomas, T lymphocytes activated by H. pylori are responsible for B-cell proliferation ( 106 ).…”