RECOMBINATION BETWEEN AN EXPRESSED IMMUNOGLOBULIN HEAVY-CHAIN GENE AND A GERMLINE VARIABLE GENE SEGMENT IN A LY-1+ B-CELL LYMPHOMA
RECOMBINATION BETWEEN AN EXPRESSED IMMUNOGLOBULIN HEAVY-CHAIN GENE AND A GERMLINE VARIABLE GENE SEGMENT IN A LY-1+ B-CELL LYMPHOMA
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DOI：
10.1038/322843a0
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发表时间：
1986-08-28
期刊：
影响因子：
64.8
通讯作者：
WEIGERT, M
中科院分区：
文献类型：
--
作者：
KLEINFIELD, R;HARDY, RR;WEIGERT, M
小鼠B细胞分化的早期阶段的特征在于一系列免疫球蛋白基因重排，这是从种系基因区段组装重（H）链和轻（L）链可变区所需的。重链基因座处的重排首先开始，并且由多样性（DH）基因区段与连接（JH）基因区段的连接组成。这形成了DJH中间体，随后向其添加可变（VH）基因片段。轻链基因重排发生在aVL基因片段与aJL基因片段的连接之后，由aVL基因片段与aJL基因片段的连接组成：一旦形成生产性轻链基因，细胞就会启动表面免疫球蛋白M（slgM）受体的合成（综述见参考文献1）。这些受体是克隆分布的，可能通过体细胞突变2，3或可能通过持续的重组事件4进一步多样化。已经在Ly 1+ B细胞淋巴瘤NFS-5中检测到这样的重组事件，其已经显示在形成slgM（μκ）分子之后重排λ和H链基因5。我们分析了NFS-5的生产性等位基因的重排，发现这是由于VH基因之间的一种新的重组事件，它导致原始VH_（52）重排的大部分或全部编码序列被种系VH_（7183）基因所取代。嵌入在靠近交换位点的VH编码序列中的是序列5′ TACTGTG 3′，它与许多DH基因片段5′的信号七聚体相同6。这种嵌入的七聚体在超过70%的已知VH基因中是保守的7 -17。我们认为这种七聚体介导VH基因替换，并且可能在抗体谱系的开发中发挥重要作用。
The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H)- and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (DH) gene segment to a joining (JH) gene segment. This forms aDJHintermediate to which a variable (VH) gene segment is subsequently added. Light-cháin gene rearrangement follows and consists of the joining of aVLgene segment to aJLgene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (slgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation2,3or possibly by continued recombinational events4. Such recombinational events have been detected in the Ly 1+B-cell lymphoma NFS-5, which has been shown to rearrange both λ and H-chain genes subsequent to the formation of slgM (μκ) molecules5. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event betweenVHgenes which results in the replacement of most or all of the coding sequence of the initialVHQ52 rearrangement by a germlineVH7183 gene. Embedded in theVHcoding sequence close to the site of the cross-over is the sequence 5′ TACTGTG 3′, which is identical to the signal heptamer found 5′ of manyDHgene segments6. This embedded heptamer is conserved in over 70% of knownVHgenes7–17. We suggest that this heptamer mediatesVHgene replacement and may play an important part in the development of the antibody repertoire.