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

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Abstract

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, CD 19 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 C γ2, and c-Abl, which may contribute to CD19 regulation of B cell function. CD19/Lyn complex formation also regulates phosphorylation of CD22 and FcγRIIB, which inhibit B cell signal transduction through the recruitment of the SHP1 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.

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  1. Thomas F. Tedder

    Present address: Department of Immunology, Duke University Medical Center, Box 3010, 27710, Durham, NC

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  1. Department of Immunology, Duke University Medical Center, Box 3010, 27710, Durham, NC

    Manabu Fujimoto, Jonathan C. Poe & Minoru Hasegawa

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Fujimoto, M., Poe, J.C., Hasegawa, M. et al. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol Res 22, 281–298 (2000). https://doi.org/10.1385/IR:22:2-3:281

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