IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis.
Homeostasis of human B cell development is maintained by a complex network of cytoplasmic and surface expressed molecules. Abnormalities in this process may result in the expansion of malignant B cell precursors in B lineage acute lymphoblastic leukaemia (ALL). ALL cells share surface antigens with normal early precursor B cells. We have studied here the role of Fas/APO-1 (CD95) antigen on leukaemic precursor B cell line growth and survival, and the modulation of its effects by signals involved in normal early B cell development. Four ALL cell lines representative of the early steps of B cell differentiation are shown to express surface Fas/APO-1 (CD95) antigen and to undergo apoptosis in the presence of anti-Fas cross-linking antibodies. This effect is strongly enhanced when pre-B, but not pro-B cells, are pretreated with IL-7 but not with IL-2, IL-3, IL-4 or IL-10. Furthermore, pre-B cell death induced by anti-Fas antibodies in combination with IL-7 is increased upon pre-B receptor but not CD19 cross-linking. Bcl-2 and Bax protein expression is not influenced by IL-7 or pre-BR stimulation in either pro-B or pre-B cell lines. These results indicate that signals involved in normal early B cell development can modulate the Fas (CD95)-mediated apoptosis of leukaemic precursor B cells.
Levy
Y
Y
Département d'Immunologie, Hôpital Henri Mondor, Creteil, France.
Benlagha
K
K
Buzyn
A
A
Colombel
M
M
Brouet
J C
JC
Lassoued
K
K
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D015851:Interleukin-7; D019014:fas Receptor