[Impaired CD95-(Fas,APO-1-)apoptosis regulation is a progression factor in early MALT-type lymphoma genesis].
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.


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.


CONCLUSIONS
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.
Seeberger
H
H
Pathologisches Institut, Universität Würzburg. path071@mail.uni-wuerzburg.de
Knörr
C
C
Müller-Hermelink
H K
HK
Greiner
A
A
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor
Eine gestörte CD95-(Fas,APO-1-)vermittelte Apoptoseregulation ist ein Progressionsfaktor in der frühen MALT-Typ-Lymphomgenese.