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The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia
Author(s) -
Fournier S.,
Yang L. P.,
Delespesse G.,
Rubio M.,
Biron G.,
Sarfati M.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb03314.x
Subject(s) - cd23 , b cell , gene isoform , biology , lymphokine , cytokine , interleukin 4 , immunology , microbiology and biotechnology , antigen , antibody , immunoglobulin e , gene , biochemistry
Summary. B lymphocytes from chronic lymphocytic leukaemia (B‐CLL) patients express the two CD23 isoforms (type A and B), which differ only in their intracytoplasmic domain. The abnormal regulation of the CD23 antigen in response to IL‐4, IFNs α and γ results in CD23 over‐expression on B‐CLL cells. Our present study shows that the two CD23 isoforms are differentially and abnormally regulated on B‐CLL cells. IL‐4 selectively up‐regulates CD23 type A mRNA in five different B‐CLL patients, whereas in normal B cells it enhances CD23 type A and is the most potent inducer of type B. In contrast, phorbol esters (PMA) up‐regulate both CD23 isoforms in the malignant B cells and specifically increases type B in normal B cells. We next postulated that cytokines other than IL‐4 regulate CD23 B isoform in B‐CLL cells and therefore examined the effect of IL‐2, IFN‐γ and IFN‐α. We found that the ability of a given cytokine to induce B‐CLL growth (i.e. IL‐2 and IFNα) is concurrent with a selective up‐regulation of CD23 type B mRNA, whereas lymphokines that have no B cell growth activity (i.e. IL‐4 and IFNγ) specifically increase CD23 type A mRNA. We next showed that IL‐4 and IFNγ prevent hydrocortisone‐induced programmed cell death and that the rescued malignant B cells mainly express CD23 type A. Given that CD23 molecule has been reported to play a role in normal B cell proliferation and survival, it is therefore proposed that in B‐CLL cells the expression of CD23 type A may be related to cell viability and that of type B to cell proliferation. These data suggest that the CD23 molecule may contribute to the physiopathology of the disease which is characterized by the accumulation of long‐lived and slow‐dividing monoclonal B cells.