LOSS OF TRANSFORMING GROWTH-FACTOR-BETA-1 REGULATORY ACTIVITY IN HUMAN NON-HODGKIN LYMPHOMAS

Since TGF beta 1 inhibits the proliferation of normal B-cells, its dis turbed activity in B cell lymphomas is conceivable. We found high expr ession of TGF beta 1 mRNA in three human B cell non-Hodgkin lymphoma x enografts; also, the gene product (in latent form) was detectable in a ll lymphoma cells. However, on exposing the cells to exogenously activ ated TGF beta 1, the incorporation of tritiated thymidine decreased in normal (murine thymocytes, human peripheral mononuclear cells), but n ot in lymphoma cells. These observations suggest the malfunction of TG F beta 1 mediated regulatory pathway (e.g. insufficient activation or receptor expression) which can contribute to the unlimited expansion o f a lymphoid clone. The opposite expression of c-myc to TGF beta and t he retained sensitivity to anti-IgM indicate that c-myc and Ig recepto r can operate independently of TGF beta in the regulation of lymphoid cell proliferation.