Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice
Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice
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DOI：
10.1073/pnas.050580697
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发表时间：
2000-03-28
影响因子：
11.1
通讯作者：
Hsu, HL
中科院分区：
文献类型：
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作者：
Khare, SD;Sarosi, I;Hsu, HL
TALL-1/Blys/BAFF是肿瘤坏死因子（TMF）配体超家族的成员，在功能上参与B细胞增殖。在这里，我们描述了在β -肌动蛋白启动子控制下表达TALL-1的转基因小鼠的B细胞增生和自身免疫性狼疮样变化。由于B220+细胞数量的增加，TALL-1转基因小鼠表现出严重的脾脏、淋巴结和Peyer's斑块肿大。由于血清IgM、IgG、IgA和IgE的升高，转基因小鼠也出现了高γ球蛋白血症。此外，在TALL-1转基因小鼠中也发现了类似自身免疫性狼疮样疾病的表型，其特征是存在针对核抗原的自身抗体和肾脏中的免疫复合物沉积。转基因B细胞的存活时间延长和过度活跃可能导致这些动物的自身免疫性狼疮样表型。我们的研究进一步证实了TALL-1作为B细胞的刺激因子影响Ig的产生。因此，TALL-1可能是B细胞相关自身免疫性疾病的主要介质。
TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TMF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupuslike changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE, In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.