Mantle cell lymphoma proliferates upon IL-10 in the CD40 system

Mantle cell lymphoma (MCL) is a B cell non-Hodgkin's lymphoma, characterize d by a poor response to therapy and short survival. To assess the prolifera tive capacity, we cultured MCL cells, using irradiated 3T6 mouse fibroblast s transfected with human CD40L ('CD40 system') in the presence of different cytokines. Proliferation was measured by H-3-thymidine incorporation and b y CFSE fluorescence. Thirteen out of 16 MCL cases proliferated well in the CD40 system. In 10 cases a strong response upon further addition of IL-10 w as seen, whereas IL-4 had an additional effect in only four cases. CFSE sta ining of cells before and after culture showed an increased number of cell divisions in the IL-10/CD40L stimulated cells. The MCL cells remained CD5()CD19(+). Neither plasma cell differentiation nor isotype switching was see n. The light chain expression was strictly monoclonal. IL-1 beta, IL-2, IL- 6, G-CSF and GM-CSF did not stimulate MCL proliferation. IL-10 receptor exp ression correlated with the response to IL-10 in the culture system and the effect of added IL-10 could be blocked by antibodies directed against IL-1 0 and the IL-10 receptor. Autocrine IL-10 production by the MCL cells was d etected in eight of 10 cases tested. IL-10 receptor blocking decreased prol iferation when no exogenous IL-10 was used in four of seven cases tested. E BV assessed by EBER in situ hybridization was not detected in six cases tes ted. In conclusion, MCL can successfully be cultured upon CD40 stimulation if 3T6 CD40L(+) cells are used. In this context IL-10 is a costimulatory fa ctor. IL-10 receptor expression seems to correlate with response to CD40 cr osslinking and IL-10. Autocrine IL-10 production might play a role in the p roliferation of this lymphoma. This culture system may be useful to test ne w treatment strategies for this, thus far, therapy-resistant lymphoma.