SEQUENCE HOMOLOGIES, N-SEQUENCE INSERTION AND JH GENE UTILIZATION IN VHDJH JOINING - IMPLICATIONS FOR THE JOINING MECHANISM AND THE ONTOGENIC TIMING OF LY1-B CELL AND B-CLL PROGENITOR GENERATION
SEQUENCE HOMOLOGIES, N-SEQUENCE INSERTION AND JH GENE UTILIZATION IN VHDJH JOINING - IMPLICATIONS FOR THE JOINING MECHANISM AND THE ONTOGENIC TIMING OF LY1-B CELL AND B-CLL PROGENITOR GENERATION
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DOI：
10.1002/j.1460-2075.1990.tb07382.x
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发表时间：
1990-07-01
期刊：
影响因子：
11.4
通讯作者：
RAJEWSKY, K
中科院分区：
文献类型：
--
作者：
GU, H;FORSTER, I;RAJEWSKY, K
对来自个体发育不同阶段的B谱系细胞的重排VHDJH基因的序列分析表明，重组断点处的短序列同源性有助于V区基因组装。这种同源性经常出现在新生儿前B细胞的DJH连接处，其中大多数不含N序列。在相同的细胞，但不是在以后的发展阶段，优先使用的JH 1元素被观察到。出生后，N序列插入随着时间的推移而增加，并且总是在VHD边界比DJH边界更突出。在来自成年动物的前B细胞和成熟B细胞中，在N序列不可检测的情况下，仅在一半的情况下发现DJH边界处的序列同源性。这种较低的发生率可能是由于N序列添加到重组DNA末端之一和/或细胞选择。检查VHDJH连接处的N序列插入、DJH边界处的序列同源性和JH 1的使用允许估计个体发育中特定B细胞亚群接种到免疫系统中的时间点。具体而言，本数据显示Ly 1 B细胞亚群的细胞不仅在出生时产生，而且在出生后的第一周产生。然而，源自相同B细胞亚群的慢性B细胞白血病的祖细胞的DJH连接与新生儿前B细胞的DJH连接相似，表明这些细胞在该早期发育阶段已经经历了转化事件。
Sequence analysis of rearranged VHDJH genes of B lineage cells from various stages of ontogeny indicates that short sequence homologies at the breakpoints of recombination contribute to V region gene assembly. Such homologies are regularly seen at DJH junctions of neonatal pre-B cells, most of which do not contain N sequences. In the same cells, but not at later developmental stages, preferential usage of the JH1 element is observed. After birth, N sequence insertion increases with time and is always more prominent at the VHD border than the DJH border. In pre-B cells from adult animals and in mature B cells, in cases where N sequences were not detectable, sequence homologies at the DJH border were found in only half of the instances. This lower incidence could be due to N sequence addition to one of the recombining DNA ends and/or cellular selection. Inspection of VHDJH junctions for N sequence insertion, sequence homologies at the DJH border and JH1 usage allows the estimation of the timepoint in ontogeny at which particular B cell subsets are seeded into the immune system. Specifically, the present data show that the cells of the Ly1 B cell subset are generated not only neonatally but also beyond the first weeks of life. However, the DJH junctions of the progenitors of chronic B cell leukemias which originate from the same B cell subset resemble those of neonatal pre-B cells, suggesting that these cells have already undergone a transforming event at this early developmental stage.