Activation and accumulation of B cells in TACI-deficient mice

The tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLy S) binds two TNF receptor family members, transmembrane activator and calci um-modulating and cyclophilin ligand interactor (TACI) and B cell maturatio n molecule (BCMA). Mice that are transgenic for BLyS show a cell accumulati on, activation and autoimmune lupus-like nephritis. The existence of at lea st two distinct BLyS receptors raises the question of the relative contribu tion of each to B cell functions. We therefore generated mice that were def icient in TACI, TACI(-/-) mice showed increased a cell accumulation and mar ked splenomegaly. isolated TACI(-/-) B cells hyperproliferated and produced increased amounts of immunoglobulins in vitro. In vivo antigen challenge r esulted in enhanced antigen-specific antibody production. Thus, TACI may pl ay an unexpected inhibitory role in a cell activation that helps maintain i mmunological homeostasis.