Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis.
We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.
Griffiths
S D
SD
Leukaemia Research Fund Centre, Institute of Cancer Research, London, United Kingdom.
Goodhead
D T
DT
Marsden
S J
SJ
Wright
E G
EG
Krajewski
S
S
Reed
J C
JC
Korsmeyer
S J
SJ
Greaves
M
M
D000512:Alpha Particles; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D003907:Dexamethasone / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011005:Plutonium; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014965:X-Rays
D015851:Interleukin-7; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011005:Plutonium; D005047:Etoposide; D003907:Dexamethasone; D003513:Cycloheximide; D002945:Cisplatin