IL-6 contributes to the expression of RAGS in human mature B cells
IL-6 contributes to the expression of RAGS in human mature B cells
复制标题
DOI：
10.4049/jimmunol.179.10.6790
复制
发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Jamin, Christophe
中科院分区：
文献类型：
--
作者：
Hillion, Sophie;Dueymes, Maryvonne;Jamin, Christophe
成熟的B细胞获得了修改次级淋巴器官中重排的Ig V区基因的能力。在之前的研究中，我们证明了BCR和CD40的交联诱导了RAG1和RAG2酶的表达，从而导致了二次重排。我们在此研究RAG1和RAG2在外周和扁桃体B细胞表达的机制。BCR和CD40的协同作用促进了IL-6的合成，从而上调其受体在活化的B淋巴细胞上的表达。此外，我们提供的证据表明，IL-6启动循环B细胞中rag的表达，并扩展其在扁桃体B细胞中的表达。因此，中和IL-6或阻断其受体可抑制RAG的表达。此外，我们证明IL-6阻碍bcr介导的RAG基因表达终止在两种B细胞群体中。IL-6受体阻断对RAG基因转录的恢复抑制支持了一旦重组启动，其终止也受IL-6调控的观点。综上所述，这些研究为IL-6在诱导和终止成熟人B细胞二次重排重组酶机制表达中的双重作用提供了新的见解。
Mature B cells acquire the capacity to revise rearranged Ig V region genes in secondary lymphoid organs. In previous studies, we demonstrated that cross-linking the BCR and the CD40 induces the expression of the RAG1 and RAG2 enzymes and, thereby, secondary rearrangements. We examine herein the mechanism that underpins RAG1 and RAG2 expression in peripheral and tonsil B cells. Coordinated engagement of the BCR and CD40 promoted the synthesis of IL-6 and, thereby, up-regulation of its receptor on activated B lymphocytes. Furthermore, we provide evidence that IL-6 initiates the expression of RAGS in circulating B cells, and extends those in tonsil B cells. Thus, neutralization of IL-6 or blocking of its receptor inhibits RAG expression. Moreover, we demonstrate that IL-6 impedes BCR-mediated termination of RAG gene expression in both population of B cells. The recovered inhibition of RAG gene transcription by IL-6 receptor blockade supports the notion that once recombination is launched, its termination is also regulated by IL-6. Taken together, these studies provide new insight into the dual role of IL-6 in inducing and terminating expression of the recombinase machinery for secondary rearrangements in mature human B cells.