Hillion Sophie, Youinou Pierre, Jamin Christophe
Laboratory of Immunology Brest University Medical School, BP 824, F29609 Brest, France.
Autoimmun Rev. 2007 Jun;6(6):415-20. doi: 10.1016/j.autrev.2007.01.002. Epub 2007 Feb 2.
Establishment of the B cell repertoire is regulated by recombination activating genes RAG1 and RAG2 proteins in the bone marrow. Tolerance of autoreactivity is mainly prevented by receptor editing, i.e. synthesis of a new B cell receptor following re-expression of RAG1 and RAG2. Numerous signals can lead to RAG up-regulation, all in association with soluble cytokines. In the periphery, autoreactive B cells or low-affinity B cell receptor synthesis may appear following antigenic immune response. Receptor revision, i.e. new immunoglobulin gene rearrangement can participate to the control of these lymphocytes following new RAG1 and RAG2 re-induction. Though signals leading to this peripheral RAG up-regulation are poorly described, IL-6 seems to have a preponderant role. Therefore, the elevated levels of IL-6 secreted by activated B cells in systemic lupus erythematosus might contribute to the maintenance of abnormal RAG expression, and in turn may participate to the emergence of autoreactive B cells in the periphery.
B细胞库的建立在骨髓中受重组激活基因RAG1和RAG2蛋白调控。自身反应性的耐受性主要通过受体编辑来预防，即RAG1和RAG2重新表达后合成新的B细胞受体。许多信号可导致RAG上调，所有这些都与可溶性细胞因子有关。在外周，抗原免疫应答后可能出现自身反应性B细胞或低亲和力B细胞受体合成。受体修正，即新的免疫球蛋白基因重排，可在新的RAG1和RAG2重新诱导后参与对这些淋巴细胞的控制。尽管导致外周RAG上调的信号描述较少，但IL-6似乎起主要作用。因此，系统性红斑狼疮中活化B细胞分泌的IL-6水平升高可能有助于维持异常的RAG表达，进而可能参与外周自身反应性B细胞的出现。
