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Abstract
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.