ORDERED REARRANGEMENT OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION SEGMENTS
ORDERED REARRANGEMENT OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION SEGMENTS
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DOI：
10.1002/j.1460-2075.1984.tb01955.x
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发表时间：
1984-01-01
期刊：
影响因子：
11.4
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
ALT, FW;YANCOPOULOS, GD;BALTIMORE, D
IG H链可变区编码为生殖系DNA中3个独立的元件文库：VH、D和JH。为了检查它们连接的顺序和调节，开发了区分它们的各种组合的测定，并且该测定用于研究B淋巴细胞的肿瘤细胞类似物以及正常B淋巴细胞。Abelson鼠白血病病毒（A-MuLV）转化的胎肝细胞，可用于分析的最原始的B淋巴样细胞类似物，通常在两个JH基因座上都有DJH重排。这些细胞系在培养物中继续DNA重排，在大多数情况下，通过将VH基因片段连接到现有的DJH复合物上，同时删除插入的DNA序列。这些品系或其后代均未显示VHD或DD重排的证据。产生H链的肿瘤细胞系代表B细胞途径的更成熟阶段，正常B淋巴细胞在其2个H链位点处具有2个VHDJH重排或VHDJH重排加上DJH重排;它们也没有表现出VHD或DD重排的证据。这些结果支持一个有序的机制，可变基因组装在B细胞分化过程中，D-到-JH重排通常首先发生，然后在两个染色体上的VH-到-DJH重排，与两种类型的连接过程中发生的染色体内缺失。在H链产生系中，特别是在正常B淋巴细胞中，保留在DJH构型中的JH等位基因的高百分比支持H链等位基因排斥的调节机制，其中VHDJH重排，如果是生产性的，防止另外的VH到DJH重排。
The Ig H chain variable region is encoded as 3 separate libraries of elements in germ-line DNA: VH, D and JH. To examine the order and regulation of their joining, assays were developed that distinguish their various combinations and the assays were used to study tumor cell analogs of B-lymphoid cells as well as normal B-lymphoid cells. Abelson murine leukemia virus (A-MuLV) transformed fetal liver cells, the most primitive B-lymphoid cell analog available for analysis, generally had DJH rearrangements at both JH loci. These lines continued DNA rearrangement in culture, in most cases by joining a VH gene segment to an existing DJH complex with the concomitant deletion of intervening DNA sequences. None of these lines or their progeny showed evidence of VHD or DD rearrangements. H chain-producing tumor lines, representing more mature stages of B-cell pathway, and normal B-lymphocytes had either 2 VHDJH rearrangements of VHDJH plus a DJH rearrangement at their 2 H chain loci; they also showed no evidence of VHD or DD rearrangements. These results support an ordered mechanism of variable gene assembly during B-cell differentiation in which D-to-JH rearrangements generally occur first and on both chromosomes followed by VH-to-DJH rearrangements, with both types of joining processes occurring by intrachromosomal deletion. The high percentage of JH alleles remaining in the DJH configuration in H chain-producing lines and, especially, in normal B-lymphocytes supports a regulated mechanism of H chain allelic exclusion in which a VHDJH rearrangement, if productive, prevents an additional VH-to-DJH rearrangement.