| First Author | Qian Y | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 4 | Pages | 575-87 |
| PubMed ID | 15485634 | Mgi Jnum | J:93923 |
| Mgi Id | MGI:3510272 | Doi | 10.1016/j.immuni.2004.09.001 |
| Citation | Qian Y, et al. (2004) Act1, a negative regulator in CD40- and BAFF-mediated B cell survival. Immunity 21(4):575-87 |
| abstractText | 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. |
