STAT6 and the regulation of CD23 expression in B-chronic lymphocytic leukemia

High CD23 expression is a hallmark of B-CLL cells. It is lost during in vit ro culture and can be reinduced by IL-4, albeit to a lower extent than in n ormal B cells. To elucidate the events controlling CD23 expression in B-CLL cells, the IL-4 mediated induction of STAT6 was investigated. Western-blot analysis demonstrated that B-CLL cells contain comparable amounts of STAT6 . Electrophoretic mobility shift assays (EMSA) showed no constitutive nucle ar translocation of STAT6. IL-4 induced the translocation of STAT6 in B-CLL cells from all 22 patients investigated. The increase was transient, dose and time dependent without a distinct difference between B-CLL cells and no n-malignant B cells. However, in contrast to normal B lymphocytes no strict correlation between CD23 expression and STAT6 activation was detected in B -CLL. Therefore further signalling pathways and transcription factors in ad dition to STAT6 have to be activated to explain the high expression of CD23 in B-CLL cells. For example, STAT1 which is induced by IFN-gamma and binds to the classical STAT6 site. It might be involved in the strong induction of CD23 on B-CLL cells after cotreatment with IL-4 and IFN-lr, while in non -malignant B lymphocytes IFN-y leads to a reduction of IL-4 mediated CD23 e xpression. (C) 2000 Elsevier Science Ltd. All rights reserved.