Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements
Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements
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DOI：
10.1016/s1074-7613(03)00030-x
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发表时间：
2003-02-01
期刊：
影响因子：
32.4
通讯作者：
Sen, R
中科院分区：
文献类型：
--
作者：
Chowdhury, D;Sen, R
免疫球蛋白重链（IgH）蛋白的产生反馈以终止进一步的V-H基因重组，这种现象也称为等位基因排斥。在这里，我们提供的证据来支持这一命题，等位基因排斥是终止信号激活V-H基因重组的后果。对于最大的V（H）J558基因家族，这通过减弱前B细胞中的IL-7/IL-7 R信号而发生。这些信号的丢失使V-H基因座恢复到与低乙酰化历史相关的染色质状态，并且核酸酶不易接近。此外，通过激活该途径，未重排的V-H基因的超乙酰化和可及性可以在等位基因排除的脾B细胞中恢复。因此，在发育过程中，瞬时信号介导V-H基因的激活和失活。
Production of immunoglobulin heavy chain (IgH) protein feeds back to terminate further V-H gene recombination, a phenomenon also referred to as allelic exclusion. Here we provide evidence to support the proposition that allelic exclusion is the consequence of terminating signals that activate V-H genes for recombination. For the largest V(H)J558 family of genes, this occurs by attenuating IL-7/IL-7R signals in pre-B cells. Loss of these signals reverts the V-H locus to a chromatin state that is associated with hypoacetylated histories and is less accessible to nucleases. Furthermore, hyperacetylation and accessibility of unrearranged V-H genes can be restored in allelically excluded splenic B cells by activating this pathway. Thus, transient signals mediate V-H gene activation and inactivation during development.