Murine B Cell Response to TLR7 Ligands Depends on an IFN-beta Feedback Loop

作者：Green Nathaniel M; Laws Amy; Kiefer Kerstin; Busconi Liliana; Kim You Me; Brinkmann Melanie M; Trail Erin Hodges; Yasuda Kei; Christensen Sean R; Shlomchik Mark J; Vogel Stefanie; Connor John H; Ploegh Hidde; Eilat Dan; Rifkin Ian R; van Seventer Jean Maguire; Marshak Rothstein Ann^*

来源：The Journal of Immunology, 2009, 183(3): 1569-1576.

DOI：10.4049/jimmunol.0803899

Type I IFNs play an important, yet poorly characterized, role in systemic lupus erythematosus. To better understand the interplay between type I IFNs and the activation of autoreactive B cells, we evaluated the effect of type I IFN receptor (IFNAR) deficiency in murine B cell responses to common TLR ligands. In comparison to wild-type B cells, TLR7-stimulated IFNAR(-/-) B cells proliferated significantly less well and did not up-regulate costimulatory molecules. By contrast, IFNAR1(-/-) B cells did not produce cytokines, but did proliferate and up-regulate activation markers in response to other TLR ligands. These defects were not due to a difference in the distribution of B cell populations or a failure to produce a soluble factor other than a type I IFN. Instead, the compromised response pattern reflected the disruption of an IFN-beta feedback loop and constitutively low expression of TLR7 in the IFNAR1(-/-) B cells. These results highlight subtle differences in the IFN dependence of TLR7 responses compared with other TLR-mediated B cell responses. The Journal of Immunology, 2009, 183: 1569-1576.

• 出版日期2009-8-1