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[Impaired CD95-(Fas,APO-1-)apoptosis regulation is a progression factor in early MALT-type lymphoma genesis]
H Seeberger1, C Knörr, H K Müller-Hermelink
1Pathologisches Institut, Universität Würzburg. path071@mail.uni-wuerzburg.de
Background:
MALT-type lymphomas are B cell tumors arising for so far unknown reasons on the background of chronic inflammation, e.g. Helicobacter pylori-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 cell 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 survival of B cells was measured by FACS analysis.
Results:
Activated T cells induced CD95 expression and thus enhanced sensitivity to CD95L-mediated apoptosis in normal memory B cells. However, malignant B cells from 3 out of 7 low-grade MALT-type lymphomas and all 4 gastric DLBLs resisted apoptosis, although the 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 prolonged survival. This phenomenon acts as a progression factor in early lymphomagenesis.