Restricted association of V and J-C gene segments for mouse lambda chains.
Restricted association of V and J-C gene segments for mouse lambda chains.
复制标题
小鼠 lambda 链的 V 和 J-C 基因片段的限制性关联。
DOI：
10.1073/pnas.81.8.2484
复制
发表时间：
1984
影响因子：
11.1
通讯作者：
Eisen,HN
中科院分区：
文献类型：
--
作者：
Reilly,EB;Blomberg,B;Imanishi-Kari,T;Tonegawa,S;Eisen,HN
在30个小鼠B细胞系中，通过Southern印迹杂交检测可变（V）λ与连接（J）λ基因片段的不同重排的频率，每个细胞系产生已知亚型（λ 1、λ 2或λ 3）的免疫球蛋白λ轻链。对于12个λ 1链中的11个，重排是V λ 1-J λ 1;对于9个λ 2链中的9个，重排是V λ 2-J λ 2;对于9个λ 3链中的8个，重排是V λ 1-J λ 3。通过考虑其他44条λ链在氨基酸或cDNA水平上的部分或完整序列，获得了类似的结果（前24名）：对于这些链中的43条，重排的V-J基因片段对于28条λ 1链明显为V λ 1-J λ 1，对于10条λ 2链明显为V λ 2-J λ 2，对于5个λ 3链，V λ 1-J λ 3。在总共74条链中，有3条具有不寻常的V λ重排，全部涉及V λ 2基因片段：对于这些不寻常的链中的2条，编码片段为V λ 2-J λ 1-C λ 1，对于1条，编码片段为V λ 2-J λ 3-C λ 3。因此，所有74条λ链的结果表明，与κ链的明显不受限制的V κ-J κ重排相反，对于3种鼠λ链亚型中的每一种，V-J重组都受到严格限制：在λ 1和λ 3链中表达的V λ基因片段几乎总是V λ 1（分别为95%和93%），而在λ 2链中，无一例外地是V λ 2（19条链中的19条）。因此，V-λ-J λ组合变异不是近交系小鼠λ链氨基酸序列多样性的重要来源。如果λ基因片段的顺序是5 ′ V λ 2-J λ 2C λ 2 J λ 4C λ 4-V λ 1-J λ 3C λ 3 J λ 1C λ 1 3 ′，如先前和本发现所建议的，似乎（i）当V λ基因片段在发育中的B细胞中重排时，它通常与最近下游（3 '）的J λ基因片段重组，J λ C λ片段的簇，和（ii）V λ重排到上游（5 '）簇是非常罕见的，并且可能根本不发生。
The frequencies of diverse rearrangements of variable (V)lambda to joining (J)lambda gene segments were examined by Southern blot hybridization in 30 murine B-cell lines, each producing an immunoglobulin lambda light chain of known subtype (lambda 1, lambda 2, or lambda 3). For 11 out of 12 lambda 1 chains, the rearrangement was V lambda 1----J lambda 1; for 9 out of 9 lambda 2 chains, it was V lambda 2----J lambda 2; and for 8 out of 9 lambda 3 chains, it was V lambda 1----J lambda 3. Similar results were obtained by considering the partial or complete sequences at the amino acid or cDNA level of 44 other lambda chains (24 previously described): for 43 of these chains the rearranged V-J gene segments were evidently V lambda 1-J lambda 1 for 28 lambda 1 chains, V lambda 2-J lambda 2 for 10 lambda 2 chains, and V lambda 1-J lambda 3 for 5 lambda 3 chains. Of the combined total of 74 chains there were 3 with unusual V lambda rearrangements, all involving the V lambda 2 gene segment: for 2 of these unusual chains, the encoding segments were V lambda 2-J lambda 1-C lambda 1 and for one they were V lambda 2-J lambda 3-C lambda 3. Thus, the results for all 74 lambda chains show that, in contrast to the apparently unrestricted V kappa----J kappa rearrangements for kappa chains, for each of the 3 murine lambda-chain subtypes V-J recombination is severely restricted: the V lambda gene segment expressed in lambda 1 and lambda 3 chains was nearly always V lambda 1 (95% and 93%, respectively), whereas in lambda 2 chains it was without exception V lambda 2 (19 out of 19 chains). Therefore V lambda-J lambda combinatorial variation is not a significant source of amino acid sequence diversity of lambda chains of inbred mice. If the order of the lambda gene segments is 5' V lambda 2-J lambda 2C lambda 2J lambda 4C lambda 4-V lambda 1-J lambda 3C lambda 3J lambda 1C lambda 1 3', as suggested previously and by the present findings, it appears that (i) when a V lambda gene segment rearranges in a developing B cell it ordinarily recombines with a J lambda gene segment in the nearest downstream (3') cluster of J lambda C lambda segments, and (ii) V lambda rearrangement to the upstream (5') cluster is very rare and possibly may not take place at all.