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

Abstract 

High CD23 expression is a hallmark of B-CLL cells. It is lost during in vitro culture and can be reinduced by IL-4, albeit to a lower extent than in normal 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 nuclear 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 non-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 addition 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-γ 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-γ, while in non-malignant B lymphocytes IFN-γ leads to a reduction of IL-4 mediated CD23 expression.

Keywords: CLL, STAT6, CD23, IL-4, Signal transduction

Abbreviations: mAb, monoclonal antibody, CLL, chronic lymphocytic leukemia, EMSA, electrophoretic mobility shift assay, IL, interleukin, IFN, interferon, IL-4RE, interleukin-4 responsive element, JAK, janus kinase, PMA, phorbol-myristate-acetate, STAT, signal transducer and activator of transcription.