Ability of IgH isotype-switch in mature B-cell leukemias : a diagnostic application

成熟 B 细胞白血病中 IgH 同型转换的能力：诊断应用

基本信息

批准号：
11670188
负责人：
KAYANO Hidekazu
金额：
$ 0.77万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Isotype switch (IS) of immunoglobulin (Ig) heavy chain is essential for B-cell maturation. In this study we analyzed IS events on neoplastic B-cells of mature B-cell leukemias (MBL) mainly from hairy cell leukemia (HCL) and its variant (HCLv).(1) MBL cells other than follicular lymphoma cells could undergo IgE-switch induced by anti-CD40 antibody stimuli.(2)HCL and HCLv express Ig heavy chains in a divergent pattern. Hairy cells were analyzed for the presence of de-methylation of promoter sequence of IS-related genes that may indicate their activities. The cyclin D1 promoter sequence was de-methylated in 50% of HCL but none of HCLv. While de-methylation of the PAX5 promoter sequence was found in 16% of HCL and 67% of HCLv, suggesting difference in activation state between HCL and HCLv, although patterns of expression of Ig heavy and light chains were not different between HCL and HCLv.(3)Somatic mutation analysis of Ig-heavy chain (VH) genes of hairy cells showed correlation between IgG expression and VH mutation frequency. The expression of Ig lambda chain was also correlated with VH mutation frequency. Thus, it is suggested that the mutation activity of the VH gene have influence on Ig expression of hairy cells.(4)In contrast, mutation analysis of Ig light chain (VL) genes of hairy cells showed no correlation between VL and VH mutation frequency, or the expression patterns of Ig heavy or light chains, suggesting the expression of Ig light chains on hairy cells are regulated by transcription or translation but not the genetic level.Collectively, the expression of Ig chains on hairy cells may reflect different stages of B-maturation and/or activation. HCL/HCLv may provide a human model for the pathway of B-cell maturation.

免疫球蛋白（IG）重链的同种型开关（IS）对于B细胞成熟至关重要。在这项研究中，我们分析了主要来自毛细胞白血病（HCl）及其变异（HCLV）的成熟B细胞白血病（MBL）的肿瘤B细胞。（1）MBL细胞以外的MBL细胞以外的卵泡淋巴瘤细胞而不是抗CD40抗体刺激性刺激性刺激性A型（2）Hcl（2）Hcl。图案。分析了毛状细胞，以存在可能表明其活性的IS相关基因的启动子序列的脱甲基化。细胞周期蛋白D1启动子序列在50％的HCL中被脱甲基，但没有HCLV。尽管在HCl的16％和67％的HCLV中发现了PAX5启动子序列的脱甲基化，但表明HCl和HCLV之间的激活状态差异差异，尽管Ig重和轻度链的表达模式在HCL和HCLV的表达模式之间并没有差异。 Ig Lambda链的表达也与VH突变频率相关。因此，有人提出，VH基因的突变活性对毛细胞的Ig表达有影响。（4）与毛细胞的Ig光链（VL）基因的突变分析显示，VL和VH突变频率之间没有相关性，或者是遗传链的表达，而不是遗传链的表达，而不是遗传链的表达，而不是遗传链的表达。 Ig链在毛细胞上的表达可能反映了B饱和和/或激活的不同阶段。 HCL/HCLV可以为B细胞成熟途径提供人体模型。