J. Exp. Med., Volume 186, Number 11, December 1, 1997 1897-1910

Qualitative Regulation of B Cell Antigen Receptor Signaling by CD19: Selective Requirement for PI3-Kinase Activation, Inositol-1,4,5-Trisphosphate Production and Ca²⁺ Mobilization

By Anne Mette Buhl,^* Christopher M. Pleiman,^§ Robert C. Rickert, and John C. Cambier^*

From the ^* Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206;  Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206; ^§ Cadus Pharmaceuticals, 1601 Pierce St., Suite 110, Lakewood, Colorado 80214; and  Department of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0322

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.

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