BAFF activates NF-κB in gastric DLBCL (MALT) lymphoma cells via the classic pathway as well as an alternative pathway. The classic pathway (I) up-regulates BCL10, and AKT phosphorylates BCL10, leading to the formation of BCL10/BCL3 complexes that translocate to the nucleus. The alternate pathway (II), in conjunction with the classic pathway, induces BAFF expression and NF-κB activation. BAFF is also produced by monocytes, macrophages, dendritic cells, and some T cells, and its expression can be up-regulated by inflammatory cytokines that are present in the microenvironment of the stomach (pathway III). These findings suggest that BAFF production by tumor cells or gastric microenvironments can result in long-term NF-κB activation by forming a positive feedback loop, thereby contributing to the H pylori–independent growth of gastric DLBCL (MALT).