Nature Immunology
2, 638 - 643 (2001)
doi:10.1038/89790
Activation and accumulation of B cells in TACI-deficient miceMinhong Yan1, Hua Wang2, Betty Chan2, Meron Roose-Girma1, Sharon Erickson1, Thad Baker2, Daniel Tumas2, Iqbal S. Grewal2
& Vishva M. Dixit11
Department of Molecular Oncology, Genentech Inc., San Francisco, CA 94080, USA. 2
Department of Immunology, Genentech Inc., San Francisco, CA 94080, USA.
Correspondence should be addressed to Vishva M. Dixit dixit@gene.com or Iqbal S. Grewal iqbal@gene.comThe tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLyS) binds two TNF receptor family members, transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI) and B cell maturation molecule (BCMA). Mice that are transgenic for BLyS show B cell accumulation, activation and autoimmune lupus-like nephritis. The existence of at least two distinct BLyS receptors raises the question of the relative contribution of each to B cell functions. We therefore generated mice that were deficient in TACI. TACI-/- mice showed increased B cell accumulation and marked splenomegaly. Isolated TACI-/- B cells hyperproliferated and produced increased amounts of immunoglobulins in vitro. In vivo antigen challenge resulted in enhanced antigen-specific antibody production. Thus, TACI may play an unexpected inhibitory role in B cell activation that helps maintain immunological homeostasis.
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