Nishizumi H, Taniuchi I, Yamanashi Y, Kitamura D, Ilic D, Mori S, Watanabe T, Yamamoto T
Department of Oncology, Institute of Medical Science, University of Tokyo, Japan.
Immunity. 1995 Nov;3(5):549-60. doi: 10.1016/1074-7613(95)90126-4.
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 lymphoblast-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.
Src家族蛋白酪氨酸激酶Lyn与BCR存在物理关联，并且有人提出它在BCR介导的信号传导中发挥重要作用。对lyn-/-小鼠的研究表明，其外周组织中的B细胞数量减少了一半。此外，这些B细胞对包括BCR交联和CD40配体在内的多种刺激没有正常反应。在这些B细胞中，BCR交联后对多种细胞蛋白（如Vav、Cbl和HS1）的酪氨酸磷酸化诱导也被消除。尽管BCR介导的信号传导受损，但lyn-/-小鼠血清中的IgM和IgA浓度显著升高，并且检测到自身抗体的产生。组织学研究显示，突变小鼠随着年龄增长出现脾肿大和淋巴结肿大。脾脏中含有大量浆细胞以及携带Mac1抗原和细胞质IgM的异常淋巴母细胞样细胞。这些细胞在体外自发分泌大量IgM。最后，大量lyn-/-小鼠出现肾小球肾炎，这是自身免疫性疾病的一个迹象。根据这些数据，我们得出结论，Lyn不仅在外周B细胞的克隆扩增和终末分化的信号转导中起作用，而且在自身反应性B细胞的清除中也起作用。
