CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification.

Journal Article (Journal Article;Review)

The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are interpreted and modified by response regulators such as CD19 that govern mature B cell activation. The current understanding of how CD19 governs B lymphocyte signaling is outlined in this review. Primarily, CD19 establishes a novel Src-family kinase amplification loop that regulates basal signal transduction thresholds in resting B cells. Moreover, CD19 amplifies Src-family kinase activation following BCR ligation. CD19 amplification of Lyn activity leads to processive phosphorylation of CD19 and downstream substrates including CD22. Phosphorylated CD19 recruits other effector molecules including Vav, Grb2, phosphoinositide 3-kinase, phospholipase Cgamma2, and c-Abl, which may contribute to CD19 regulation of B cell function. CD19/Lyn complex formation also regulates phosphorylation of CD22 and FcgammaRIIB, which inhibit B cell signal transduction through the recruitment of the SHPI and SHIP phosphatases. These observations provide insight into how CD19 governs the molecular ordering and intensity of signals transduced in B cells, and how perturbations in CD19 expression or signaling function may contribute to autoimmunity.

Full Text

Duke Authors

Cited Authors

  • Fujimoto, M; Poe, JC; Hasegawa, M; Tedder, TF

Published Date

  • 2000

Published In

Volume / Issue

  • 22 / 2-3

Start / End Page

  • 281 - 298

PubMed ID

  • 11339363

International Standard Serial Number (ISSN)

  • 0257-277X

Digital Object Identifier (DOI)

  • 10.1385/IR:22:2-3:281


  • eng

Conference Location

  • United States