Impaired CD95 (Fas, APO-1)-mediated apoptosis is a progression factor of early MALT-type lymphomagenesis

Background: MALT-type lymphomas are B cell tumors arising for so far unknow n reasons an the background of chronic inflammation, e.g. Helicobacter pylo ri-associated gastritis. T cells are supposed to have a positive impact on tumor growth, but fail in their control function. We therefore examined the interaction of T cells with malignant B cells in vitro and focused on T ce ll control which normally operates by CD95L/CD95-mediated apoptosis. Patients and Methods: malignant B cells were isolated from tumor tissues of 7 patients with low-grade MALT-type:lymphoma and 4 patients with DLBL and cocultured in vitro with activated T cells. Normal memory B cells were used as control. We developed a T/B coculture assay for investigation of CD95L/ CD95-mediated apoptosis. The influence of T cells on CD95 expression and su rvival of B cells was measured by FACS analysis. Results: Activated T cells induced CD95 expression and thus enhanced sensit ivity to CD95L-mediated apoptosis in normal memory B cells. However, malign ant B cells from 3 out of low-grade MALT-type lymphomas and all 4 gastric D LBLs resisted apoptosis, although thr cells showed enhanced CD95 expression . Conclusion: Resistance to CD95L/CD95-mediated apoptosis allows malignant B cells from MALT-type lymphoma to escape T cell control and leads to prolong ed survival. This phenomenon acts as a progression factor in early lymphoma genesis.