Dorsch M, Goff S P
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13131-6. doi: 10.1073/pnas.93.23.13131.
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.
原癌基因c-abl编码一种细胞功能未知的非受体酪氨酸激酶。为了研究c-Abl在早期B细胞增殖、分化和细胞周期调控中的可能作用，从c-abl缺陷小鼠及其野生型同窝小鼠建立了长期淋巴细胞骨髓培养物。突变型和野生型小鼠均可产生表达B220和CD43的白细胞介素7依赖性祖B细胞克隆和细胞系。通过对不同浓度白细胞介素7的反应中胸苷掺入量测定，突变型和野生型细胞系的增殖能力没有差异。同样，c-abl缺陷并不影响突变克隆在体外分化为表面IgM阳性细胞的能力。然而，生长因子剥夺后对培养物的分析显示，c-abl突变细胞中细胞死亡速度显著加快，末端脱氧核苷酸转移酶介导的UTP缺口末端标记分析证实这是由于凋亡所致。此外，糖皮质激素处理后，c-abl突变细胞对凋亡性细胞死亡也更敏感。这些结果表明，突变型c-Abl使B细胞祖细胞对凋亡更敏感，这可能解释了在c-abl缺陷动物中观察到的一些表型。
