Abl-mediated transformation, immunoglobulin gene rearrangements and arrest of B lymphocyte differentiation.
Abl-mediated transformation, immunoglobulin gene rearrangements and arrest of B lymphocyte differentiation.
复制标题
Abl 介导的转化、免疫球蛋白基因重排和 B 淋巴细胞分化停滞。
DOI：
10.1182/blood.v82.7.2062.2062
复制
发表时间：
1994
影响因子：
14.5
通讯作者：
N. Rosenberg
中科院分区：
文献类型：
--
作者：
N. Rosenberg
ABL癌基因最初是在Abelson病毒中发现的，Abelson病毒是一种小鼠逆转录病毒。这种病毒和ABL编码的蛋白酪氨酸激酶以其转化B淋巴细胞前体细胞的能力而闻名。大多数转化的细胞类似于正常的B系祖细胞，称为前B细胞，似乎在免疫球蛋白轻链基因重排阶段的分化受阻。使用温度敏感型Abelson病毒突变体获得的最新证据直接支持了这一观点。由一种这种病毒转化的淋巴样细胞在转变到不允许的温度后不久进行轻链重排。这一事件伴随着几个与轻链基因重排相关的经典变化，包括核因子-kappa B转录因子活性增加，轻链RNA表达以及RAG-1和RAG-2基因表达水平增加。虽然ABL蛋白阻断这些因子活性的机制尚不清楚，但这些数据表明，酪氨酸磷酸化可能与调节早期B细胞发育和对抗原受体基因重排的所有阶段至关重要的基因的表达密切相关。
The abl oncogene was originally discovered in Abelson virus, a murine retrovirus. This virus and the protein tyrosine kinase encoded by abl are well known for their ability to transform B lymphocyte progenitors. Most of the transformed cells resemble a normal B lineage progenitor called a pre-B cell and appear to be arrested in differentiation at the stage of immunoglobulin light chain gene rearrangement. Recent evidence obtained using temperature-sensitive Abelson virus mutants provides direct support for this idea. Lymphoid cells transformed by one such virus undergo light chain rearrangement soon after shift to the nonpermissive temperature. This event is accompanied by several changes classically associated with light chain gene rearrangement including increased activity of the NF-kappa B transcription factor, expression of light chain RNAs and increased levels of expression of the RAG-1 and RAG-2 genes. Although the mechanism by which abl protein blocks the activity of these factors is not yet known, these data suggest that tyrosine phosphorylation may be intimately connected to regulation of early B cell development and expression of genes that are central to all phases of antigen receptor gene rearrangement.