Immunity 2003 Feb;18(2):279-88
Loss of TACI Causes Fatal Lymphoproliferation and Autoimmunity, Establishing TACI as an Inhibitory BLyS Receptor.
Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS.
Department of Immunology, Genentech, Inc., 1 DNA Way, 94080, South San Francisco, CA, USA
BLYS, A KEY CYTOKINE THAT SUSTAINS B CELL MATURATION AND TOLERANCE, BINDS THREE RECEPTORS: BR3, BCMA, and TACI. Results from knockout mice implicate a major functional role for BR3 and a redundant one for BCMA in B cell function. TACI's role is controversial based on defects in TI antibody responses accompanied by B cell hyperplasia in knockout mice. We have presently characterized a precise role for TACI in vivo. TACI(-/-) mice develop fatal autoimmune glomerulonephritis, proteinurea, and elevated levels of circulating autoantibodies. Treatment of B cells with TACI agonistic antibodies inhibits proliferation in vitro and activation of a chimeric receptor containing the TACI intracellular domain induces apoptosis. These results demonstrate the critical requirement for TACI in regulating B cell homeostasis.
(I believe, but do not know, that TACI is the Zymogenetics nomenclature. Pseudo Biologist knows this story.) |
