Li X, Sandoval D, Freeberg L, Carter R H
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
J Immunol. 1997 Jun 15;158(12):5649-57.
CD19 and CD21, which form a complex on B lymphocytes, are required for normal Ab responses to T-dependent Ags. Coligation of the CD21/CD19 complex with membrane IgM (mIgM) powerfully enhances B cell activation in vitro and in vivo. To determine how CD19-mIgM synergy is produced, we examined immediate and downstream signaling events after ligation of either complex alone or after CD19-mIgM coligation in normal and lymphoblastoid B cells. Ligation of mIgM alone is known to result in tyrosine phosphorylation of CD19 and association of CD19 with phosphatidylinositol 3-kinase and Vav, and these events are not enhanced by coligation. In contrast, tyrosine phosphorylation of phosphatidylinositol 3-kinase and Vav is markedly enhanced after CD19-mIgM coligation. Coligation also results in synergistic, prolonged enhancement of mitogen-activated protein kinase activity, relative to ligation of either receptor complex alone. Mutation of CD19 Y391, the site at which Vav binds, but not mutation of CD19 Y482 and Y513, the sites of association with phosphatidylinositol 3-kinase, blocks the enhancement of mitogen-activated protein kinase activation. These findings suggest that the synergistic enhancement of B cell activation following CD19-mIgM coligation results from greater tyrosine phosphorylation of Vav and Vav-dependent enhanced activation of mitogen-activated protein kinases.
CD19和CD21在B淋巴细胞上形成复合物，是对T细胞依赖性抗原产生正常抗体反应所必需的。CD21/CD19复合物与膜IgM（mIgM）的共结合在体外和体内均能有力地增强B细胞活化。为了确定CD19-mIgM协同作用是如何产生的，我们检测了正常和淋巴母细胞样B细胞中单独连接任一复合物或CD19-mIgM共连接后即刻及下游的信号转导事件。已知单独连接mIgM会导致CD19的酪氨酸磷酸化以及CD19与磷脂酰肌醇3激酶和Vav的结合，而这些事件不会因共连接而增强。相反，CD19-mIgM共连接后磷脂酰肌醇3激酶和Vav的酪氨酸磷酸化显著增强。相对于单独连接任一受体复合物，共连接还会导致丝裂原活化蛋白激酶活性的协同、持续增强。Vav结合位点CD19 Y391的突变，而非与磷脂酰肌醇3激酶结合位点CD19 Y482和Y513的突变，会阻断丝裂原活化蛋白激酶激活的增强。这些发现表明，CD19-mIgM共连接后B细胞活化的协同增强是由于Vav酪氨酸磷酸化增加以及Vav依赖性丝裂原活化蛋白激酶的激活增强所致。
