Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor

Immunity. 2003 Feb;18(2):279-88. doi: 10.1016/s1074-7613(03)00025-6.


BLys , a key cytokine that sustains B cell maturation and tolerance, binds three receptors: BR3, BCMA, and TACI. Results from knockout mice implicate a major functional role for BR3 and a redundant one for BCMA in B cell function. TACI's role is controversial based on defects in TI antibody responses accompanied by B cell hyperplasia in knockout mice. We have presently characterized a precise role for TACI in vivo. TACI(-/-) mice develop fatal autoimmune glomerulonephritis, proteinurea, and elevated levels of circulating autoantibodies. Treatment of B cells with TACI agonistic antibodies inhibits proliferation in vitro and activation of a chimeric receptor containing the TACI intracellular domain induces apoptosis. These results demonstrate the critical requirement for TACI in regulating B cell homeostasis.

MeSH terms

  • Animals
  • Apoptosis
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cell Differentiation
  • Glomerulonephritis, Membranoproliferative / genetics
  • Glomerulonephritis, Membranoproliferative / immunology
  • Glomerulonephritis, Membranoproliferative / pathology
  • Humans
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / immunology*
  • Lymphoproliferative Disorders / pathology
  • Membrane Proteins*
  • Mice
  • Mice, Knockout
  • Phenotype
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / deficiency*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Transmembrane Activator and CAML Interactor Protein


  • B-Cell Activation Factor Receptor
  • BLyS receptor
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF13B protein, human
  • TNFRSF13C protein, human
  • Tnfrsf13b protein, mouse
  • Tnfrsf13c protein, mouse
  • Transmembrane Activator and CAML Interactor Protein