Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor

被引:320
作者
Seshasayee, D
Valdez, P
Yan, MH
Dixit, VM
Tumas, D
Grewal, IS
机构
[1] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA
关键词
D O I
10.1016/S1074-7613(03)00025-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:279 / 288
页数:10
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