Abstract
Genetic ablation of the B cell surface glycoprotein CD19 severely impairs the humoral immune response. This requirement is thought to reflect a critical role of CD19 in signal transduction that occurs upon antigen C3dg coligation of antigen receptors with CD19 containing type 2 complement receptors (CR2). Here we show that CD19 plays a key accessory role in B cell antigen receptor signaling independent of CR2 coligation and define molecular circuitry by which this function is mediated. While CD19 is not required for antigen-mediated activation of receptor proximal tyrosines kinases, it is critical for activation of phosphatidylinositol 3-kinase (PI3-kinase). PI3-Kinase activation is dependent on phosphorylation of CD19 Y484 and Y515. Antigen-induced CD19-dependent PI3-kinase activation is required for normal phosphoinositide hydrolysis and Ca2+ mobilization responses. Thus, CD19 functions as a B cell antigen receptor accessory molecule that modifies antigen receptor signaling in a qualitative manner.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Androstadienes / pharmacology
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Animals
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Antigens, CD19 / chemistry
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Antigens, CD19 / genetics
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Antigens, CD19 / physiology*
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Binding Sites
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Calcium / physiology*
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DNA, Complementary / genetics
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Enzyme Inhibitors / pharmacology
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Extracellular Space / metabolism
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Humans
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Inositol 1,4,5-Trisphosphate / biosynthesis
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Inositol 1,4,5-Trisphosphate / physiology*
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Intracellular Fluid / metabolism
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Mast-Cell Sarcoma / pathology
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Mice
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Mutagenesis, Site-Directed
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptors, Antigen, B-Cell / physiology*
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Recombinant Fusion Proteins / physiology
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Signal Transduction / physiology*
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Spleen / cytology
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Tumor Cells, Cultured
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Wortmannin
Substances
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Androstadienes
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Antigens, CD19
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DNA, Complementary
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Enzyme Inhibitors
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Receptors, Antigen, B-Cell
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Recombinant Fusion Proteins
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Inositol 1,4,5-Trisphosphate
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Phosphatidylinositol 3-Kinases
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Protein-Tyrosine Kinases
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Calcium
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Wortmannin