The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia.
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 alpha and gamma 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-gamma and IFN-alpha. We found that the ability of a given cytokine to induce B-CLL growth (i.e. IL-2 and IFN alpha) 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 IFN-gamma) specifically increase CD23 type A mRNA. We next showed that IL-4 and IFN gamma 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.
Fournier
S
S
Allergy Research Laboratory, Notre-Dame Hospital Research Center, Montreal, Quebec, Canada.
Yang
L P
LP
Delespesse
G
G
Rubio
M
M
Biron
G
G
Sarfati
M
M
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology*; D015152:Blotting, Northern; D002455:Cell Division; D002470:Cell Survival; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007519:Isoantigens / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics*; D015854:Up-Regulation
D007519:Isoantigens; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4; D007371:Interferon-gamma