Increased sensitivity to apoptotic stimuli in c-abl-deficient progenitor B-cell lines.
The protooncogene c-abl encodes a nonreceptor tyrosine kinase whose cellular function is unknown. To study the possible involvement of c-Abl in proliferation, differentiation, and cell cycle regulation of early B cells, long-term lymphoid bone marrow cultures were established from c-abl-deficient mice and their wild-type littermates. Interleukin 7-dependent progenitor B-cell clones and lines expressing B220 and CD43 could be generated from both mutant and wild-type mice. The mutant and wild-type lines displayed no difference in their proliferative capacity as measured by thymidine incorporation in response to various concentrations of interleukin 7. Similarly, c-abl deficiency did not interfere with the ability of mutant clones to differentiate into surface IgM-positive cells in vitro. Analysis of cultures after growth factor deprivation, however, revealed a strikingly accelerated rate of cell death in c-abl mutant cells, due to apoptosis as confirmed by terminal deoxynucleotidyltransferase-mediated UTP nick end labeling analysis. Furthermore, a greater susceptibility to apoptotic cell death in c-abl mutant cells was also observed after glucocorticoid treatment. These results suggest that mutant c-Abl renders the B-cell progenitors more sensitive to apoptosis, and may account for some of the phenotypes observed in c-abl-deficient animals.
Dorsch
M
M
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Goff
S P
SP
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D016313:Genes, abl; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015851:Interleukin-7 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051917:Leukosialin; D008213:Lymphocyte Activation; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000032:analysis
D015703:Antigens, CD; D015851:Interleukin-7; D051917:Leukosialin; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D017493:Leukocyte Common Antigens