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 (TN F) superfamily. BLyS stimulates proliferation of, and immunoglobulin produc tion by, B cells. However, the relative importance of BLyS in physiological B cell activation is unclear. We identified a B cell receptor for BLyS thr ough expression cloning as TACI, an orphan TNF receptor homologue of unknow n function. Binding of BLyS to TACI activated signaling by nuclear factor-k appa B (NF-kappa). In vitro soluble TACI-Fc fusion protein blocked BLyS-ind uced NF-kappa B activation in B lymphoma cells and IgM production in periph eral blood B cells. In vivo treatment of immunized mice with TACI-Fc inhibi ted production of antigen-specific IgM and IgG I antibodies and abolished s plenic germinal center (GC) formation.-rhus, BLyS activity must play a crit ical role in the humoral immune response.