Moon Byoung-gon, Takaki Satoshi, Nishizumi Hirofumi, Yamamoto Tadashi, Takatsu Kiyoshi
Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Cell Immunol. 2004 Apr;228(2):110-8. doi: 10.1016/j.cellimm.2004.04.005.
Lyn, the src-family protein tyrosine kinase, plays a crucial role in the regulation of B cell antigen receptor (BCR)- and IL-5-receptor (IL-5R)-mediated signaling. Lyn-deficient mice have been reported to exhibit an increase in B-1 cell numbers, splenomegaly and accumulation of lymphoblast-like cells in the spleen with age, resulting in hyperimmunoglobulinemia and glomerulonephritis caused by the deposition of autoantibody complexes. To elucidate the role of IL-5 in B-1 cell activation, autoantibody production and autoimmune diseases, Lyn-deficient mice were crossed with IL-5Ralpha chain (IL-5Ralpha)-deficient mice and generated Lyn- and IL-5Ralpha-deficient (DKO) mice. In contrast to Lyn-deficient mice, DKO mice showed significantly reduced splenomegaly and lymphoadenopathy and reduced B-1 cell number in the peritoneal cavity. DKO mice also secreted low levels of IgM and IgG autoantibodies. Biochemical and histological analyses revealed that DKO mice showed milder pathogenesis of autoimmune-like disorders than Lyn-deficient mice. These results suggest involvement of IL-5 in enhanced B-1 cell activation, autoantibody production, and development of autoimmune disease in Lyn-deficient mice.
Src家族蛋白酪氨酸激酶Lyn在调节B细胞抗原受体（BCR）和白细胞介素-5受体（IL-5R）介导的信号传导中起关键作用。据报道，Lyn缺陷小鼠随着年龄增长，B-1细胞数量增加、脾脏肿大且脾脏中出现成淋巴细胞样细胞积聚，导致自身抗体复合物沉积引起的高免疫球蛋白血症和肾小球肾炎。为了阐明IL-5在B-1细胞活化、自身抗体产生和自身免疫性疾病中的作用，将Lyn缺陷小鼠与IL-5Rα链（IL-5Rα）缺陷小鼠杂交，培育出Lyn和IL-5Rα双缺陷（DKO）小鼠。与Lyn缺陷小鼠相比，DKO小鼠的脾脏肿大和淋巴结病明显减轻，腹腔中的B-1细胞数量减少。DKO小鼠还分泌低水平的IgM和IgG自身抗体。生化和组织学分析表明，与Lyn缺陷小鼠相比，DKO小鼠自身免疫样疾病的发病机制较轻。这些结果提示IL-5参与了Lyn缺陷小鼠中B-1细胞活化增强、自身抗体产生及自身免疫性疾病的发展。
