DOWN-REGULATION OF RAG1 AND RAG2 GENE-EXPRESSION IN PREB CELLS AFTER FUNCTIONAL IMMUNOGLOBULIN HEAVY-CHAIN REARRANGEMENT
DOWN-REGULATION OF RAG1 AND RAG2 GENE-EXPRESSION IN PREB CELLS AFTER FUNCTIONAL IMMUNOGLOBULIN HEAVY-CHAIN REARRANGEMENT
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DOI：
10.1016/1074-7613(95)90131-0
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发表时间：
1995-11-01
期刊：
影响因子：
32.4
通讯作者：
WINKLER, TH
中科院分区：
文献类型：
--
作者：
GRAWUNDER, U;LEU, TMJ;WINKLER, TH
在B细胞发育过程中，两波免疫球蛋白基因重排，首先是重链基因重排，然后是轻链基因重排，形成功能性免疫球蛋白基因。在小鼠骨髓中，B220(CD45R)、c-kit、CD25和替代轻链的不同表面表达以及细胞周期状态允许FACS分离发生这两波重排的细胞。两个重组激活基因RAG1和RAG2的基因产物在这一重排过程中起着至关重要的作用，在这里，我们发现RAG基因的表达在转录水平上是两次上调和下调，RAG2蛋白在转录水平上是在转录后水平上表达的。在D-->；J(H)和V-H->；DJ(H)重排Prob和Preb-I细胞中高表达，在细胞表面表达Preb细胞受体的Preb细胞中低表达，在V-L->；J(L)重排小Preb-II细胞中高表达，在未成熟B细胞中RAG1和RAG2mRNA表达下调，而RAG2蛋白表达保持不变。一个重链等位基因发生重排后，RAG1和RAG2基因表达下调可能是阻止另一个重链等位基因进一步重排的部分机制。
Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the light chain gene loci form functional immunoglobulin genes during B cell development. In mouse bone marrow the differential surface expression of B220 (CD45R), c-kit, CD25, and surrogate light chain as well as the cell cycle status allows FACS separation of the cells in which these two waves of rearrangements occur. The gene products of two recombination activating genes, RAG1 and RAG2 are crucial for this rearrangement process, Here, we show that the expression of the RAG genes is twice up- and down-regulated, at the transcriptional level for RAG1 and RAG2, and at the postranscriptional level for RAG2 protein. Expression levels are high in D --> J(H) and V-H --> DJ(H) rearranging proB and preB-I cells, low in preB cells expressing the preB cell receptor on the cell surface, and high again in V-L --> J(L) rearranging small preB-II cells, In immature B cells expressing on the cell surface RAG1 and RAG2 mRNA is down-regulated, whereas RAG2 protein levels are maintained. Downregulation of RAG1 and RAG2 gene expression after productive rearrangement at one heavy chain allele might be part of the mechanisms that prevent further rearrangements at the other allele.