Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity.
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.
Yan
M
M
Department of Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Marsters
S A
SA
Grewal
I S
IS
Wang
H
H
Ashkenazi
A
A
Dixit
V M
VM
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D053264:B-Cell Activating Factor; D019556:COS Cells; D003001:Cloning, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha