Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI

BLyS (also called TALL-1, THANK, or BAFF) 1] 2] 3] 4] is a member of the tumor necrosis factor (TNF) gene family that stimulates proliferation and immunoglobulin production by B cells. BLyS interacts with the TNF receptor (TNFR) homologue TACI (transmembrane activator and CAML-interactor) 5], and treatment of mice with a TACI-Fc fusion protein abolishes germinal center formation after antigenic challenge 6]. Here we report a novel interaction between BLyS and another TNFR homologue, BCMA (B cell maturation antigen) 7] 8]. Further, the TNF homologue APRIL 9], a close relative of BLyS, also bound to BCMA and TACI. BLyS or APRIL activated nuclear factor-kappaB (NF-kappaB) through TACI and BCMA, and each ligand stimulated immunoglobulin M (IgM) production by peripheral blood B cells. These results define a dual ligand-receptor system that may play an important role in humoral immunity.