Abstract
B ymphocyte 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-κB (NF-κB). In vitro soluble TACI-Fc fusion protein blocked BLyS-induced NF-κB 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 IgG1 antibodies and abolished splenic germinal center (GC) formation. Thus, BLyS activity must play a critical role in the humoral immune response.
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Acknowledgements
We thank Laura Closkey, Tina Etchevery, Robert Pitti, Mark Nagel, Phil Haas for help with recombinant protein expression and purification, James Lee for cDNA libraries, Wyne Lee for help with animal studies, and Genentech's DNA sequencing and DNA synthesis labs.
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Yan, M., Marsters, S., Grewal, I. et al. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat Immunol 1, 37–41 (2000). https://doi.org/10.1038/76889
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DOI: https://doi.org/10.1038/76889
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