Functional interaction of the gp80 and gp130 IL-6 receptors in human B cell malignancies

IL-6, or cytokines of the IL-6 family using gp130 as transducer chain recep tor, have been suggested to play a role in certain B lymphoid neoplasia. Th e presence of cell membrane gp80 and gp130 IL-6 receptors was studied in 98 patients with various leukaemia and non-Hodgkin's malignant lymphoma using flow cytofluorometry and immunohistology. Except neoplasia of immature B c ells which expressed neither of the receptors, the majority of B cell tumou rs expressed one or both of them, mantle cell lymphoma being found to expre ss the highest density of receptors. Using IL-6-dependent XG myeloma cell l ines and mAb recognizing various gp80 and gp130 functional epitopes, it has been shown that IL-6 activation leads to a modified expression of some epi topes. In particular, the decrease or the disappearance of a gp130 epitope called Al signed gp130 dimerization which is the first step of the gp130 ac tivation pathway. Gp80 and gp130 epitope analysis was achieved in 17 of the patients. In four, an epitope phenotype compatible with a cytokine-induced activation was found. The cells of five B-CLL patients which expressed bot h gp80 and gp130 receptors were incubated with IL-6 to induce activation. I n three of the cases they were found to rearrange their receptors in activa ted forms but not in the two others, showing that cells able to be activate d or not can be found. These results confirm that gp130 signalling might pl ay an important role in the pathogenesis of certain B cell neoplasia.