IFNγ induces epigenetic programming of human T-bet B cells and promotesTLR7/8 and IL-21 induced differentiation.

08:00 EDT 15th May 2019 | BioPortfolio

Summary of "IFNγ induces epigenetic programming of human T-bet B cells and promotesTLR7/8 and IL-21 induced differentiation."

Although B cells expressing the IFNgR or the IFNg-inducible transcription factor T-bet drive autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role for IFNg signaling in human antibody responses is unknown. We show that elevated levels of IFNg in SLE patients correlate with expansion of the T-bet expressing IgDCD27CD11cCXCR5 (DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naïve B cells form T-bet pre-ASCs following stimulation with either Th1 cells or with IFNg, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced by IFNg or IFNg-producing T cells. IFNg promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic reprogramming of B cells, which results in increased chromatin accessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of and loci. Finally, we show that IFNg signals poise B cells to differentiate by increasing their responsiveness to IL-21.


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This article was published in the following journal.

Name: eLife
ISSN: 2050-084X


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