Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity

Nat Immunol. 2000 Jul;1(1):37-41. doi: 10.1038/76889.


B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) superfamily. BLyS stimulates proliferation of, and immunoglobulin production by, B cells. However, the relative importance of BLyS in physiological B cell activation is unclear. We identified a B cell receptor for BLyS through expression cloning as TACI, an orphan TNF receptor homologue of unknown function. Binding of BLyS to TACI activated signaling by nuclear factor-kappa B (NF-kappa B). In vitro soluble TACI-Fc fusion protein blocked BLyS-induced NF-kappa B activation in B lymphoma cells and IgM production in peripheral blood B cells. In vivo treatment of immunized mice with TACI-Fc inhibited production of antigen-specific IgM and IgGI antibodies and abolished splenic germinal center (GC) formation. Thus, BLyS activity must play a critical role in the humoral immune response.

MeSH terms

  • Animals
  • Antibody Formation / immunology*
  • B-Cell Activating Factor
  • COS Cells
  • Cloning, Molecular
  • Humans
  • Membrane Proteins / immunology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / immunology*
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor-alpha / immunology*


  • B-Cell Activating Factor
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor
  • TNFSF13B protein, human
  • Tumor Necrosis Factor-alpha