PROLIFERATION OF B-CELL MALIGNANCIES IN ALL STAGES OF DIFFERENTIATIONUPON STIMULATION IN THE CD40 SYSTEM

Stimulation of the CD40 antigen on normal B cells by crosslinking of a nti-CD40 mAbs via their Fc receptor using a Fc gamma RII(CD32)-transfe cted mouse fibroblast cell line ('CD40 system') results in activation and proliferation. Not only normal B cells, but also malignant B cells fitting in the low-grade malignancy category such as chronic lymphocy tic leukemia (CLL), hairy cell leukemia and follicular lymphoma could be induced to proliferation upon CD40 stimulation. Here, the 'CD40 sys tem' has also been used to culture intermediate and high grade maligna ncies. Proliferation was measured by H-3-thymidine incorporation and c ell counting after culture. Time curves showed that at day 7 most cult ures were optimal. By flow cytometry, morphology and assessment of lig ht chain restriction the monoclonal nature of the cultured B cells was proven. We confirmed that B cell malignancies with a more slowly evol ving course, such as CLL (n = 11), PLL (n = 5), and low-grade NHL (imm unocytoma and follicular cb/cc n = 9), could successfully be cultured in the 'CD40 system'. In contrast, four out of seven cases of mantle c ell lymphoma did not proliferate. Cases of precursor B lineage ALL (n = 7), high grade NHL (n = 3) and multiple myeloma (n = 10) showed a he terogenous growth pattern. We conclude that the 'CD40 system', althoug h not always successful, is a useful tool to culture a whole variety o f B cell malignancies