Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia.
Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia.
复制标题
人重链可变区基因家族在家族性慢性淋巴细胞白血病中非随机重排。
DOI：
10.1073/pnas.84.23.8563
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发表时间：
1987
影响因子：
11.1
通讯作者：
Blattner,F
中科院分区：
文献类型：
--
作者：
Shen,A;Humphries,C;Tucker,P;Blattner,F
我们已经确定了一个人类免疫球蛋白重链可变区（VH）基因家族，其中一个成员在一个父亲和五个兄弟姐妹中的四个患上慢性淋巴细胞白血病的家庭的两个受影响成员中重排。对三名患病兄弟姐妹白血病淋巴细胞重排VH基因的克隆和测序表明，两名兄弟姐妹重排VH基因（VHTS1和VHWS1）同源性为90%。相应的种系基因VH251被发现是一个小的（四个基因）VH基因家族的一部分，我们称之为VHV。DNA序列与VHWS1（95%）和VHTS1（88%）的同源性以及VH 5'侧相同的限制性内切位点证实了VH251重排后的体细胞突变在两个兄弟姐妹中产生相同的VH基因重排。VHTS1不是功能性VH基因；在该患者的另一条染色体上发现功能性VH重排。另外两个兄弟姐妹有不同的VH基因重排。它们都使用了不同的多样性基因。单个VH基因的非随机选择机制包括VH基因重排的发育调控或VH基因重排的B细胞亚群的选择。
We have identified a family of human immunoglobulin heavy-chain variable-region (VH) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged VH genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged VH genes (VHTS1 and VHWS1) that were 90% homologous. The corresponding germ-line gene, VH251, was found to be part of a small (four gene) VH gene family, which we term VHV. The DNA sequence homology to VHWS1 (95%) and VHTS1 (88%) and identical restriction sites on the 5' side of VH confirm that rearrangement of VH251 followed by somatic mutation produced the identical VH gene rearrangements in the two siblings. VHTS1 is not a functional VH gene; a functional VH rearrangement was found on the other chromosome of this patient. The other two siblings had different VH gene rearrangements. All used different diversity genes. Mechanisms proposed for non-random selection of a single VH gene include developmental regulation of this VH gene rearrangement or selection of a subpopulation of B cells in which this VH has been rearranged.