RT journal article
T1 IFNγ induces epigenetic programming of human T-bethi B cells and promotes TLR7/8 and IL-21 induced differentiation
A1 Zumaquero, Esther
A1 Stone, Sara L
A1 Scharer, Christopher D
A1 Jenks, Scott A
A1 Nellore, Anoma
A1 Mousseau, Betty
A1 Rosal Vela, Antonio
A1 Botta, Davide
A1 Bradley, John E
A1 Wojciechowski, Wojciech
A1 Ptacek, Travis
A1 Danila, Maria I
A1 Edberg, Jeffrey C
A1 Bridges, S Louis
A1 Kimberly, Robert P
A1 Chatham, W Winn
A1 Schoeb, Trenton R
A1 Rosenberg, Alexander F
A1 Boss, Jeremy M
A1 Sanz, Ignacio
A1 Lund, Frances E
A2 BiomedicinaBiotecnología y Salud Pública
AB Although B cells expressing the IFNgR or the IFNg-inducible transcription factor T-betpromote autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role forIFNg signaling in human antibody responses is unknown. We show that elevated levels of IFNg inSLE 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-bethipre-ASCs following stimulation with either Th1 cells or with IFNg, IL-2, anti-Ig and TLR7/8 ligandand that IL-21 dependent ASC formation is significantly enhanced by IFNg or IFNg-producing Tcells. IFNg promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to inducegenome-wide epigenetic reprogramming of B cells, which results in increased chromatinaccessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of IL21R andPRDM1 loci. Finally, we show that IFNg signals poise B cells to differentiate by increasing theirresponsiveness to IL-21
SN 2050-084X
YR 2019
FD 2019-05-15
LK http://hdl.handle.net/10498/35094
UL http://hdl.handle.net/10498/35094
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 13-nov-2026