Heterogenous response of B lymphocytes to transforming growth factor‐beta in B‐cell chronic lymphocytic leukaemia: correlation with the expression of TGF‐β receptors
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Medientyp:
E-Artikel
Titel:
Heterogenous response of B lymphocytes to transforming growth factor‐beta in B‐cell chronic lymphocytic leukaemia: correlation with the expression of TGF‐β receptors
Beschreibung:
<jats:p>We investigated the potential role of transforming growth factor‐beta (TGF‐β) on spontaneous and cytokine‐induced proliferation of B‐cell chronic lymphocytic leukaemia (B‐CLL) cells <jats:italic>in vitro</jats:italic>. Purified B lymphocytes from 21 B‐CLL patients were cultured for 5 d in the presence of medium alone, IL‐2 and/or IL‐10, in the presence or absence of TGF‐β, and proliferation was measured by <jats:sup>3</jats:sup>H‐thymidine incorporation. TGF‐β inhibited B‐cell proliferation in the majority of patients (15/21) but no inhibition was detected in 6/21 patients whatever the type of stimulant used. Addition of neutralizing antibodies to TGF‐β increased 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, neutralizing antibodies to TGF‐β did not increase the proliferation. The expression of TGF‐β receptors on B‐CLL cells was significantly lower than the one observed on normal CD5<jats:sup>+</jats:sup> B lymphocytes for which the sensitivity to TGF‐β inhibition was more marked than in CLL. In addition, we found a strong correlation between the response of leukaemic B cells to TGF‐β inhibitory action and the expression of TGF‐β receptors on these cells. In summary, TGF‐β appears to function in CLL as a negative regulator of B lymphocytes but loss of responsiveness to this factor accompanied by a decrease of TGF‐β receptor expression, might provide a selective advantage to B‐CLL lymphocytes.</jats:p>