| First Author | de Valle E | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 4 | Pages | 621-41 |
| PubMed ID | 27022143 | Mgi Jnum | J:233073 |
| Mgi Id | MGI:5780753 | Doi | 10.1084/jem.20151182 |
| Citation | de Valle E, et al. (2016) NFkappaB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med 213(4):621-41 |
| abstractText | We examined the role of NFkappaB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFkappaB1 (Nfkappab1(-/-)) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity ofNfkappab1(-/-)Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in theNfkappab1(-/-)mice. Bone marrow chimeric mice revealed that the Fo B cell-intrinsic loss of NFkappaB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes the differentiation of Fo helper CD4(+)T cells and acts in an autocrine manner to reduce antigen receptor and toll-like receptor activation thresholds in a population of proliferating IgM(+)Nfkappab1(-/-)Fo B cells. We demonstrate that p50-NFkappaB1 repressesIl-6transcription in Fo B cells, with the loss of NFkappaB1 also resulting in the uncontrolled RELA-driven transcription ofIl-6.Collectively, our findings identify a previously unrecognized role for NFkappaB1 in preventing multiorgan autoimmunity through its negative regulation ofIl-6gene expression in Fo B cells. |
