Truncated immunoglobulin Dmu causes incomplete developmental progression of RAG-deficient pro-B cells.
Truncated immunoglobulin Dmu causes incomplete developmental progression of RAG-deficient pro-B cells.
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截短的免疫球蛋白 Dmu 会导致 RAG 缺陷的亲 B 细胞发育不完全。
DOI：
10.1016/s0161-5890(01)00085-2
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发表时间：
2002
影响因子：
3.6
通讯作者：
Alt,FrederickW
中科院分区：
文献类型：
--
作者：
Malynn,BarbaraA;Shaw,AlbertC;Young,Faith;Stewart,Valerie;Alt,FrederickW
B 细胞发育的早期阶段依赖于前 B 细胞受体 (BCR) 的表达，该受体由 μ 重链 (HC) 与替代轻链 (SLC) 蛋白以及信号分子 Igα 和 Igβ 组成。在通过体细胞基因重排形成 μ 链可变区的过程中，有时使用三个阅读框（指定为 rf2）之一将 DH 片段重排为 JH 片段，从而产生截短形式的 μ 蛋白（称为 Dμ）。当 Dμ 蛋白形成时，随后的 B 细胞发育会因进一步 HC 重排的下调而受阻，从而无法形成全长 μHC。在这项研究中，我们证明，在重组酶激活基因（RAG）-2缺陷的B220+CD43+pro-B细胞中，其中B淋巴细胞生成在C部分被阻滞，Dμ的转基因表达促进部分发育进展到C'部分，但不能介导全长μHC蛋白影响的pro-B到前B细胞向D部分的转变。这些数据表明，Dμ前BCR参与的细胞内信号传导途径不足以促进前B细胞的扩增和/或存活，并且与包含前BCR的全长μHC参与的细胞内信号传导途径不同。
Early stages of B cell development are dependent on the expression of a pre-B cell receptor (BCR), composed of a μ heavy chain (HC) in association with surrogate light chain (SLC) proteins and the signaling molecules, Igα and Igβ. During the formation of the variable region of the μ chain by somatic gene rearrangement, a truncated form of the μ protein (called Dμ) is sometimes produced by the rearrangement of a DHsegment to a JHsegment using one of three reading frames (designated rf2). When a Dμ protein is formed, subsequent B cell development is blocked by down-regulation of further HC rearrangements, so that a full-length μHC cannot be formed. In this study, we demonstrate that in recombinase activating gene (RAG)-2-deficient B220+CD43+pro-B cells in which B lymphopoiesis has been arrested at fraction C, transgenic expression of Dμ promoted partial developmental progression to fraction C′, but was unable to mediate the pro-B to pre-B cell transition to fraction D effected by full-length μHC protein. These data suggest that the intracellular signaling pathways engaged by the Dμ pre-BCR are insufficient to facilitate the expansion and/or survival of pre-B cells, and are distinct from those engaged by the pre-BCR-containing full-length μHC.