Ke, FangBenet, Zachary L.Maz, Mitra P.Liu, JianhuaDent, Alexander L.Kahlenberg, Joanne MichelleGrigorova, Irina L.2023-11-162023-11-162023-03-02Ke F, Benet ZL, Maz MP, et al. Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells. Elife. 2023;12:e83908. Published 2023 Mar 2. doi:10.7554/eLife.83908https://hdl.handle.net/1805/37086Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.en-USAttribution 4.0 InternationalFollicular regulatory T cellsGerminal center b cellsHumanImmunologic toleranceInfectious diseaseMicrobiologyMouseNuclear proteinsArticle