@misc{10498/35094,
year = {2019},
month = {5},
url = {http://hdl.handle.net/10498/35094},
abstract = {Although B cells expressing the IFNgR or the IFNg-inducible transcription factor T-bet
promote 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 IgDnegCD27negCD11c+CXCR5neg
(DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naı¨ve B cells form T-bethi
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 IL21R and
PRDM1 loci. Finally, we show that IFNg signals poise B cells to differentiate by increasing their
responsiveness to IL-21},
title = {IFNγ induces epigenetic programming of human T-bethi B cells and promotes TLR7/8 and IL-21 induced differentiation},
doi = {10.7554/ELIFE.41641},
author = {Zumaquero, Esther and Stone, Sara L and Scharer, Christopher D and Jenks, Scott A and Nellore, Anoma and Mousseau, Betty and Rosal Vela, Antonio and Botta, Davide and Bradley, John E and Wojciechowski, Wojciech and Ptacek, Travis and Danila, Maria I and Edberg, Jeffrey C and Bridges, S Louis and Kimberly, Robert P and Chatham, W Winn and Schoeb, Trenton R and Rosenberg, Alexander F and Boss, Jeremy M and Sanz, Ignacio and Lund, Frances E},
}