Helicobacter pylori and MALT Lymphoma Pedro Farinha, Randy D. Gascoyne  Gastroenterology  Volume 128, Issue 6, Pages 1579-1605 (May 2005) DOI: 10.1053/j.gastro.2005.03.083 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 H pylori and MALT lymphoma. In the stomach, H pylori do not invade the epithelium, but bind to the host epithelial cells by multiple surface adhesion molecules. Binding of the organism translocates effector proteins into both epithelial and surrounding immune cells. These cells recognize H pylori by both membrane (MHC, DC-SIGN) and intracellular (CARD4) receptors that trigger cellular apoptosis, as well as an NF-κB-dependent inflammatory response. There is infiltration of the mucosa by neutrophils and macrophages (innate immunity) followed by lymphocytes and plasma cells (adaptive immunity). The inflammation is chronic in virtually all H pylori patients, which suggests H pylori somehow hamper the host immune response through a favorable balance between T-cells subsets (helper vs regulatory cells). The persistence of inflammation triggers the acquisition of reactive MALT and leads to the formation of genotoxic agents such as ROS. The combination of H pylori strain-specific virulence factors and host immune response features (eg, different cytokine polymorphisms and components of the immune microenvironment induced by Treg cells and alternatively activated macrophages) eventually will facilitate the emergence and proliferation of a malignant B-cell clone that resembles normal memory marginal zone B cells. In early phases the survival of the malignant cells is dependent on H pylori-specific T cells and the lymphoma regresses with H pylori antibiotic therapy. Lymphoma cells can show different genomic abnormalities that proceed along 2 major pathways: (1) the H pylori-dependent pathway that shows more often a methylator phenotype and is prone to accumulate further genomic abnormalities and eventually transform into a high-grade lymphoma (DLBCL); and (2) the H pylori-independent pathway characterized by balanced translocations, the most common being t(11;18)(q32;q21), a nonmethylator phenotype, an advanced stage, and lack of response to antibiotic therapy. The t(11;18)(q32;q21) is often the only genomic abnormality found and these cases do not show clonal evolution or transformation into an aggressive lymphoma. Gastroenterology 2005 128, 1579-1605DOI: (10.1053/j.gastro.2005.03.083) Copyright © 2005 American Gastroenterological Association Terms and Conditions