Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-x(L) transgene
Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-x(L) transgene
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DOI：
10.1016/s1074-7613(00)80437-9
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发表时间：
1996-03-01
期刊：
影响因子：
32.4
通讯作者：
Behrens, TW
中科院分区：
文献类型：
--
作者：
Fang, W;Mueller, DL;Behrens, TW
在B淋巴细胞发育过程中，不能有效重排免疫球蛋白重（IgH）链等位基因的前B细胞被认为经历发育停滞和死亡，但由于这些细胞在体内寿命短，因此它们没有得到很好的表征。在B谱系中表达凋亡调节基因bcl-x（L）的转基因小鼠在骨髓中产生了大量的前B细胞扩增。在扩大的群体中，V（D）J重排几乎都是非生产性的，DJ（H）重排在D-H阅读框2中的关节和具有广泛D-H或J（H）缺失的异常关节中富集。因此，免疫球蛋白重排失败的pro-B细胞的死亡是通过凋亡发生的，bcl-x（L）可以在pro-B阶段传递强烈的存活信号。该分析还表明，免疫球蛋白基因重排不如以前认识到的精确。
During B lymphocyte development, pro-B cells that fail to rearrange an immunoglobulin heavy (IgH) chain allele productively are thought to undergo developmental arrest and death, but because these cells are short-lived in vivo they are not well characterized. Transgenic mice expressing the apoptosis regulatory gene bcl-x(L) in the B lineage developed large expansions of pro-B cells in bone marrow. V(D)J rearrangements in the expanded population were nearly all nonproductive, and DJ(H) rearrangements were enriched for joints in D-H reading frame 2 and for aberrant joints with extensive D-H or J(H) deletions. Thus, the death of pro-B cells with failed immunoglobulin rearrangements occurs by apoptosis, and bcl-x(L) can deliver a strong survival signal at the pro-B stage. This analysis also demonstrates that immunoglobulin gene rearrangement is less precise than previously appreciated.