IGG1 PLASMACYTOSIS IN INTERLEUKIN-6 TRANSGENIC MICE
IGG1 PLASMACYTOSIS IN INTERLEUKIN-6 TRANSGENIC MICE
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DOI：
10.1073/pnas.86.19.7547
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发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
KISHIMOTO, T
中科院分区：
文献类型：
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作者：
SUEMATSU, S;MATSUDA, T;KISHIMOTO, T
白介素6(IL-6)参与了多克隆性和单克隆性浆细胞异常的发病机制。为了解决这种可能性，产生了携带人IL-6基因组基因和人免疫球蛋白重链增强器融合的转基因小鼠。在所有转基因小鼠的血清中观察到高浓度的人IL-6和多克隆的IgG1增加(120-400倍)。在胸腺、淋巴结和脾中可见大量浆细胞增多，在肺、肝和肾中可见浆细胞的渗入。然而，浆细胞不能移植到同基因小鼠身上，也没有发现包括c-myc基因重排在内的染色体异常。有证据表明，IL-6基因表达失控可引发多克隆浆细胞增多，但不能诱发浆细胞瘤。提示浆细胞瘤的发生可能需要额外的基因改变。这些转基因小鼠的其他有趣发现是系膜增生性肾小球肾炎的发展和骨髓中巨核细胞的增加。
Interleukin 6 (IL-6) has been suggested to be involved in the pathogenesis of polyclonal and monoclonal plasma cell abnormalities. To address this possibility, transgenic mice carrying the human IL-6 genomic gene fused with a human immunoglobulin heavy chain enhancer were generated. High concentrations of human IL-6 and polyclonal increase in IgG1 (120- to 400-fold) in sera of all transgenic mice were observed. A massive plasmacytosis in thymus, lymph node, and spleen and an infiltration of plasma cells in lung, liver, and kidney were observed. However, the plasma cells were not transplantable to syngeneic mice and were found not to contain chromosomal aberrations including c-myc gene rearrangements. The evidence indicates that deregulated gene expression of IL-6 can trigger polyclonal plasmacytosis but cannot induce plasmacytoma. It is suggested that additional genetic changes may be required for the generation of plasma cell neoplasia. Other interesting findings in these transgenic mice were the development of mesangio-proliferative glomerulonephritis and an increase in megakaryocytes in bone marrow.