IMPAIRED PROLIFERATION OF PERIPHERAL B-CELLS AND INDICATION OF AUTOIMMUNE-DISEASE IN LYN-DEFICIENT MICE
IMPAIRED PROLIFERATION OF PERIPHERAL B-CELLS AND INDICATION OF AUTOIMMUNE-DISEASE IN LYN-DEFICIENT MICE
复制标题
DOI：
10.1016/1074-7613(95)90126-4
复制
发表时间：
1995-11-01
期刊：
影响因子：
32.4
通讯作者：
YAMAMOTO, T
中科院分区：
文献类型：
--
作者：
NISHIZUMI, H;TANIUCHI, I;YAMAMOTO, T
Src家族蛋白酪氨酸激酶林恩与BCR物理相关，并被认为在BCR介导的信号传导中起重要作用。对lyn（-/-）小鼠的研究表明，它们外周组织中的B细胞数量减少了一半。此外，这些B细胞对许多刺激（包括BCR交联和CD 40配体）没有正常反应。在这些B细胞中，在BCR交联后，对各种细胞蛋白质（如Vav、Cbl和HS 1）的酪氨酸磷酸化的诱导也被消除。尽管BCR介导的信号传导受损，但血清中IgM和IgA的浓度显著升高，并且在lyn（-/-）小鼠中检测到自身抗体的产生。组织学研究显示，突变小鼠的脾肿大和淋巴结肿大随着年龄的增长而变得明显。脾脏含有大量浆细胞以及携带Mac1抗原和胞浆IgM的不寻常的成淋巴细胞样细胞。这些细胞在体外自发分泌大量IgM。最后，大量lyn（-/-）小鼠显示肾小球肾炎，这是自身免疫性疾病的指征。从这些数据中，我们得出结论，林恩起着信号转导的作用，不仅克隆扩增和终末分化的外周B细胞，但也消除自身反应性B细胞。
The Src family protein-tyrosine kinase Lyn associates physically with the BCR and has been suggested to play an important role in BCR-mediated signaling. Studies with lyn(-/-) mice showed that the number of B cells decreased by half in their peripheral tissues. In addition, these B cells do not respond normally to a number of stimuli, including BCR cross-linking and CD40 ligand. Induction of tyrosine phosphorylation on a variety of cellular proteins, such as Vav, Cbl, and HS1, upon BCR cross-linking was also abolished in these B cells, Despite the impaired BCR-mediated signaling, concentrations of IgM and IgA in sera were remarkably elevated, and production of autoantibodies was detected in lyn(-/-) mice. Histological study showed splenomegaly and enlargement of lymph nodes that became evident with age in the mutant mice. The spleen contained significant number of plasma cells as well as unusual iymphoblast-like cells carrying Mac1 antigen and cytoplasmic IgM. These cells spontaneously secreted a large amount of IgM in vitro. Finally, significant number of lyn(-/-) mice show glomerulonephritis, an indication of autoimmune disease. From these data, we conclude that Lyn plays a role in signal transduction for not only clonal expansion and terminal differentiation of peripheral B cells but also elimination of autoreactive B cells.