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

• Main Authors: Chiara Della Bella, Maria Felicia Soluri, Simone Puccio, Marisa Benagiano, Alessia Grassi, Jacopo Bitetti, Fabio Cianchi, Daniele Sblattero, Clelia Peano, Mario Milco D’Elios
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Helicobacter pylori</i>; CagY; B cells; T cells; cytokines; MALT
• Online Access: https://www.mdpi.com/1422-0067/22/17/9459
• ISSN: 1661-6596; 1422-0067

Background: the neoplastic B cells of the <i>Helicobacter pylori</i>-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to <i>H. pylori</i>, however, the nature of the <i>H. pylori</i> antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the <i>H. pylori</i> 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 <i>H. pylori</i>–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to <i>H. pylori</i> 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 <i>H. pylori</i>-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.