English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell responses, resulting in diminished antinuclear Ab reactivity and IgG2c and IgG2b auto-Ab titers compared with B6.Sle1b mice. Additionally, we observed that the proliferation and differentiation of DNA-reactive B cells into a GC B cell phenotype require B cell-intrinsic IFN-γR signaling, suggesting that IFN-γR signaling regulates GC B cell tolerance to nuclear self-antigens. The IFN-γR deficiency, however, does not affect GC, Tfh cell, or Ab responses against T cell-dependent foreign antigens, indicating that IFN-γR signaling regulates autoimmune, but not the foreign antigen-driven, GC and Tfh cell responses. Together, our data define a novel B cell-intrinsic IFN-γR signaling pathway specific to Spt-GC development and autoimmunity. This novel pathway can be targeted for future pharmacological intervention to treat systemic lupus erythematosus.

IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity