Act1, a negative regulator in CD40- and BAFF-mediated B cell survival.
Immunity
; 21(4): 575-87, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15485634
ABSTRACT
TNF receptor (TNFR) superfamily members, CD40, and BAFFR play critical roles in B cell survival and differentiation. Genetic deficiency in a novel adaptor molecule, Act1, for CD40 and BAFF results in a dramatic increase in peripheral B cells, which culminates in lymphadenopathy and splenomegaly, hypergammaglobulinemia, and autoantibodies. While the B cell-specific Act1 knockout mice displayed a similar phenotype with less severity, the pathology of the Act1-deficient mice was mostly blocked in CD40-Act1 and BAFF-Act1 double knockout mice. CD40- and BAFF-mediated survival is significantly increased in Act1-deficent B cells, with stronger IkappaB phosphorylation, processing of NF-kappaB2 (p100/p52), and activation of JNK, ERK, and p38 pathways, indicating that Act1 negatively regulates CD40- and BAFF-mediated signaling events. These findings demonstrate that Act1 plays an important role in the homeostasis of B cells by attenuating CD40 and BAFFR signaling.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Proteínas de Transporte
/
Fator de Necrose Tumoral alfa
/
Antígenos CD40
/
Proteínas de Membrana
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article