Premium
Downregulation of the CD95 receptor and defect CD40‐mediated signal transduction in B‐chronic lymphocytic leukemia cells
Author(s) -
LaytragoonLewin N.,
Duhony E.,
Bai X.F.,
Mellstedt H.
Publication year - 1998
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1998.tb01713.x
Subject(s) - cd40 , fas receptor , apoptosis , chronic lymphocytic leukemia , tyrosine phosphorylation , signal transduction , germinal center , microbiology and biotechnology , biology , b cell receptor , tyrosine kinase , cancer research , monoclonal antibody , receptor , b cell , programmed cell death , leukemia , antibody , immunology , cytotoxic t cell , biochemistry , in vitro
Cross‐linking of the CD40 receptors has been shown to induce protein tyrosine kinases (PTK) phosphorylation and prevent apoptosis in Bcl‐2 negative germinal center B cells. The expression of CD40 on B chronic lymphocytic leukemia (B‐CLL) cells was found to be similar to that of normal B cells. Activation of normal B cells with soluble anti‐CD40 monoclonal antibody (mAb) induced tyrosine phosphorylation, prolonged survival and prevented apoptosis. However, activation of CD40 on B‐CLL cells using soluble anti‐CD40 mAb does not influence survival or apoptosis. Normal B cells entered apoptosis when cultured in the presence of soluble anti‐CD95 mAb. This process was independent of PTK activity. On B‐CLL cells, the CD95 molecules were downregulated and a transient PTK signal was observed when cross‐linking of the receptor by soluble anti‐CD95 mAb occurred. Interestingly, B‐CLL cells did not enter apoptosis in the presence of anti‐CD95 mAb. Our study indicates that survival signals mediated through the CD40 molecule and death signals mediated through the CD95 molecule used different intracellular pathways in control donor B cells. In contrast, B‐CLL cells do not respond to these signals. The leukemic B cells showed a defective CD40‐mediated signal transduction and downregulated CD95 receptor expression. As a consequence, no apoptosis could be induced in B‐CLL cells by a soluble anti‐CD95 mAb. The abnormalities of these receptors may contribute to the long‐lived status of B‐CLL cells.