B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells

  • Min Yang
    Immunobiology Center, Mount Sinai School of Medicine , New York, NY 10029
  • Hidenori Hase
    Immunobiology Center, Mount Sinai School of Medicine , New York, NY 10029
  • Diana Legarda-Addison
    Immunobiology Center, Mount Sinai School of Medicine , New York, NY 10029
  • Leena Varughese
    Immunobiology Center, Mount Sinai School of Medicine , New York, NY 10029
  • Brian Seed
    Department of Molecular Biology, Massachusetts General Hospital , Boston, MA 02114
  • Adrian T Ting
    Immunobiology Center, Mount Sinai School of Medicine , New York, NY 10029

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<jats:title>Abstract</jats:title> <jats:p>B cell maturation Ag (BCMA), a member of the TNFR superfamily expressed on B cells, binds to a proliferation-inducing ligand (APRIL) and B cell-activating factor of the TNF family (BAFF) but the specific B cell responses regulated by BCMA remain unclear. This study demonstrates that ligation of A20 B cells transfected with BCMA induces the expression of CD40, CD80/B7-1, CD86/B7-2, MHC class II, and CD54/ICAM-1, which subsequently enhances the presentation of OVA peptide Ag to DO11.10 T cells. BCMA expression in murine splenic B cells can be induced with IL-4 and IL-6, allowing subsequent treatment with APRIL or agonist anti-BCMA to similarly induce Ag presentation. A comparative analysis of hybrid receptors of TNFR2 fused to the cytoplasmic domains of APRIL/BAFF receptors found that only BCMA, but not transmembrane activator and calcium-modulator and cyclophilin ligand interactor or BAFF-R, is capable of activating Ag presentation. Although all three receptors can trigger NF-κB signaling, only BCMA activates the JNK pathway conferring on BCMA the specific ability to activate this Ag presentation response.</jats:p>

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