Common Threads of Mucosa-Associated Lymphoid Tissue Lymphoma Pathogenesis: From Infection to Translocation

Extract

In this issue of the Journal, Ferreri et al. (1) add to the growing list of infectious agents that have been associated with extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) with their finding that Chlamydia psittaci infection is associated with ocular adnexal lymphomas. Helicobacter pylori infection was first identified as a risk factor for gastric MALT lymphoma, which is invariably preceded by H. pylori-associated follicular gastritis (2). Subsequently, Isaacson et al. (2) showed that MALT lymphomas are antigen-driven clonal B-cell lymphomas and that eradication of H. pylori with antibiotic therapy could lead to lymphoma regression, at least in its early stages, prior to additional genetic events (3). More recently, Borrelia burgdorferi and Campylobacter jejuni have been linked to MALT-type lymphomas involving the skin and small intestine, respectively (4, 5). A related phenomenon may be the occurrence of essential mixed cryoglobulinemia associated with chronic hepatitis virus C infection (6). In all of these conditions, it is has been postulated that the interaction of bacterial or viral antigens with host T-cells and antigen-presenting cells leads to a complex cascade resulting in clonal B-cell or plasma cell expansion. Although all immune responses are in effect clonal, MALT lymphomas are the result of immune responses gone awry (7), in which persistence of the antigen leads eventually to an autonomous clonal proliferation. Somewhat surprisingly, it has been shown (7) that B-cell proliferation in gastric MALT lymphoma is directed at auto-antigens, and not at H. pylori.