CHARACTERIZATION OF INTERLEUKIN-10 RECEPTOR EXPRESSION ON B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS

B-cell chronic lymphocytic leukemia (B-CLL) cells accumulate in vivo i n the G(0)/G(1) phase of the cell cycle, suggesting that their maligna nt expansion is due, at least in part, to a delay in cell death. Howev er, the cellular or molecular factors responsible for a delay in B-CLL cell death are unknown. B-CLL cells do express receptors for interfer on-alpha (IFN-alpha) and IFN-gamma, and activation of both has been sh own to promote B-CLL survival in vitro by preventing apoptosis. The in terleukin-10 (IL-10) receptor is another member of the IFN receptor fa mily, but its ligand, IL-10, has been reported to induce apoptosis in B-CLL cells. In the current study, we undertook a biochemical analysis of IL-10 receptor expression on freshly isolated B-CLL cells and char acterized the functional responsiveness of IL-10 binding to its consti tutively expressed receptor. We show that B-CLL cells bind IL-10 with significant specificity and express between 47 and 127 IL-10 receptor sites per cell, with a dissociation constant in the range of 168 to 42 6 x 10(-12) mol/L. Ligand binding and activation of the IL-10 receptor expressed on B-CLL cells results in the phosphorylation of signal tra nsducer and activator of transcription 1 (STAT1) and STAT3 proteins. T his pattern of STAT protein phosphorylation is identical to IL-10 rece ptor activation on normal cells and similar to IFN-alpha (STAT1 and ST AT3) and IFN-gamma (STAT1) receptor activation in CLL. Further, in con secutive samples of fresh blood obtained from patients with B-CLL cell s, the addition of IL-10 inhibited B-CLL proliferation, enhanced B-CLL differentiation, but did not induce apoptosis. Indeed, IL-10, like IF N-gamma, was able to significantly reduce the amount of B-CLL cell dea th caused by hydrocortisone-induced apoptosis. We conclude that cytoki nes, which signal through the interferon family of receptors, have com parable functional effects on B-CLL cells. (C) 1997 by The American So ciety of Hematology.