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APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity

Nature Immunology volume 1, pages 252–256 (2000)Cite this article

Abstract

We report that the tumor neurosis factor homolog APRIL (a proliferation-inducing ligand) stimulates in vitro proliferation of primary B and T cells and increases spleen weight due to accumulation of B cells in vivo. APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-1 (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL and block APRIL-stimulated proliferation of primary B cells. BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin and Pneumovax in mice, indicating that APRIL and/or TALL-1 signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL–TALL-1 and BCMA-TACI form a two ligands–two receptors pathway involved in stimulation of B and T cell function.

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Figure 1: APRIL stimulates proliferation of primary B cells.
Figure 2: APRIL stimulates proliferation of primary T cells.
Figure 3: (a–c) APRIL binds BCMA or TACI–expressing cells.
Figure 4: Soluble BCMA-Fc and TACI-Fc block APRIL-stimulated B cell proliferation.
Figure 5: Soluble BCMA-Fc inhibits anti-KLH and anti-Pneumovax production.

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Authors and Affiliations

  1. Department of Inflammation, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1799, CA, USA

    Gang Yu, Meena Ramakrishnan, Susan McCabe, Wan-rong Qiu, Masayo Kornuc, Xing-Zhong Xia, William J. Boyle, Hailing Hsu & Lars E. Theill

  2. Department of Process Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1799 , CA, USA

    Tom Boone & John Delaney

  3. Department of Protein Chemistry, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1799 , CA, USA

    Nessa Hawkins & Michael Kelley

  4. Department of Pharmacology and Pathology, Amgen Inc. One Amgen Center Drive, Thousand Oaks, 91320-1799, CA, USA

    Jane Guo, Marina Stolina, Ildiko Sarosi & Giorgio Senaldi

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  1. Gang Yu
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Correspondence to Lars E. Theill.

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Yu, G., Boone, T., Delaney, J. et al. APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol 1, 252–256 (2000). https://doi.org/10.1038/79802

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