HETEROGENOUS RESPONSE OF B-LYMPHOCYTES TO TRANSFORMING GROWTH-FACTOR-BETA IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA - CORRELATION WITH THE EXPRESSION OF TGF-BETA RECEPTORS

We investigated the potential role of transforming growth factor-beta (TGF-beta) on spontaneous and cytokine-induced proliferation of B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. Purified B lymp hocytes from 21 B-CLL patients were cultured for 5d in the presence of medium alone, IL-2 and/or IL-10, in the presence or absence of TGF-be ta, and proliferation was measured by H-3-thymidine incorporation. TGF -beta inhibited B-cell proliferation in the majority of patients (15/2 1) but no inhibition was detected in 6/21 patients whatever the type o f stimulant used. Addition of neutralizing antibodies to TGF-beta incr eased spontaneous and cytokine-induced proliferation; this effect was dose dependent and specific because addition of an irrelevant chicken IgG had no effect on B-CLL proliferation. In resistant patients, neutr alizing antibodies to TGF-beta did not increase the proliferation. The expression of TGF-beta receptors on B-CLL cells was significantly low er than the one observed on normal CD5(+) B lymphocytes for which the sensitivity to TGF-beta inhibition was more marked than in CLL. In add ition, we found a strong correlation between the response of leukaemic B cells to TGF-beta inhibitory action and the expression of TGF-beta receptors on these cells. In summary, TGF-beta appears to function in CLL as a negative regulator of B lymphocytes but loss of responsivenes s to this factor accompanied by a decrease of TGF-beta receptor expres sion, might provide a selective advantage to B-CLL lymphocytes.