FALURE OF RECOMBINATION ACTIVATING GENE EXPRESSION OF ANATI-DNA AUTOANTIBODY SECRETING B LYMPHOCYTES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

正常成熟B淋巴细胞最近被显示为快速反应RAG蛋白。The studies suggest a role of RAG reexpressed in mature B cells for their changing Ag receptor specificity in the further maturational process of mature B lymphocytes。在这里，我们有一个表征的RAG表达的成熟B淋巴细胞。正常周围血B细胞没有快速的RAG蛋白质本身。由SAC+ IL-2和抗CD 40 + IL-4、IL-7或IL-10诱导RAGs的细胞系蛋白表达激活。RAG复合体的核转移和重组信号序列绑定活动已通过Western Blotting和一份凝胶移位测试得到验证。下游J-D2 k-D2在B细胞中使用了expressed RAG复合体。Λ光链和内拉RAGS在激活SAC+ IL-2后3-4天内同样地表达了纯化的k+B细胞，并建议对正常人类成熟B细胞中的光链基因进行重新评估。一些RAG表达B细胞，其中可能在不成功的二级重新排列通过凋亡而得到结果，由annexin V绑定证实。如果自动活性B细胞正确地快速RAG，它们将揭示其表面免疫球蛋白或将死亡，则将导致自动活性B细胞的清除。我们发现了B细胞的抗DNA自动Ab保密没有在所有情况下高速RAG，因此B细胞的保密没有通过凋亡来纠正他们的Lg基因或死亡，允许在SLE患者中自动Ab保密的开发和持久性。这些结果建议RAG反应在反DNA保密B淋巴细胞中失败可能对SLE患者的辅助保密很重要。

Normal mature B lymphocytes have recently been shown to reexpress RAG proteins. The studies suggest a role of RAG reexpressed in mature B cells for their changing Ag receptor specificity in the further maturational process of mature B lymphocytes. Here, we have characterized RAG expression of mature B lymphocytes. Normal peripheral blood B cells did not express RAG proteins spontaneously. Activation by SAC+IL-2 and anti-CD40+IL-4, IL-7, or IL-10 induced cytoplasmic expression of RAGs. Nuclear translocation and recombination signal sequence binding activity of the RAG complex were verified by Western blotting and a gel shift assay. Usage of a downstream JィイD2kィエD2 was evident in B cells having expressed RAG complex. Λ light chain and intracellular RAGs were simultaneously expressed on the purified k+B cells after activation with SAC+IL-2 for 3-4 days, suggesting rearrangement of light chain gene in normal human mature B cells. Some of RAG expressing B cells, which may have resulted in unsuccessful secondary rearrangement died via apoptosis, evidenced by annexin V binding. If autoreactive B cells express RAGs appropriately, they would revise their surface immunoglobulin or would die, leading to elimination of the autoreactive B cells. We found that anti-DNA auto Ab secreting B cells did not express RAG at all, and thus the B cells secreting anti-DNA did not revise their lg gene nor die via apoptosis, allowing development and persistence of autoAb secretion in SLE patients. These results suggest that failure of RAG reexpression in anti-DNA secreting B lymphocytes may be important for the auotAb secretion of SLE patients.