| First Author | Qian Y | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 8 | Pages | 2219-28 |
| PubMed ID | 18624351 | Mgi Jnum | J:138560 |
| Mgi Id | MGI:3805407 | Doi | 10.1002/eji.200738113 |
| Citation | Qian Y, et al. (2008) Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjogren's syndrome. Eur J Immunol 38(8):2219-28 |
| abstractText | CD40L and B lymphocyte-activating factor (BAFF), members of the TNF superfamily, play critical roles in B cell survival and activation, and in the regulation of humoral immunity. We previously reported that the adaptor molecule Act1 functions as a negative regulator of CD40- and BAFF-mediated B cell survival. Here we demonstrated that mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjogren's syndrome (SS), in association with systemic lupus erythematosus-like nephritis. Analyses of Act1(-/-)CD40(-/-) and Act1(-/-)BAFF(-/-) double-deficient mice revealed that Act1 regulates different stages of the disease development through its impact on both CD40- and BAFF-mediated pathways. We found that Act1 modulates the survival of autoreactive B cells mainly through its negative regulatory role in BAFF-mediated cell survival, while the effect of Act1 on autoantibody production is likely through modulation of CD40-mediated T cell-dependent antibody response. The impact of Act1 on both BAFF and CD40 pathways establishes Act1-deficient mice as a unique model to study distinct steps of autoimmunity and regulation of self tolerance. |
