Role of CD19 tyrosine 391 in synergistic activation of B lymphocytes by coligation of CD19 and membrane Ig.
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.
Li
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Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Sandoval
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Freeberg
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Carter
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D000818:Animals; D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D007075:Immunoglobulin M / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism / Q000502:physiology*
D018941:Antigens, CD19; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)