B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6

Abstract

Jackson et al. propose a role for B cell–intrinsic IFN-γ receptor signaling in spontaneous germinal center activation and autoantibody production.

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

“…Others have previously reported different requirements for GC formation in spontaneous autoimmunity versus deliberate immunization, with IFN-γR needed for the former but not the latter event (30,31). These observations, together with another observation that TLR7 expression in B cells is needed for GC appearance in spontaneous autoimmunity (39), are in line with our findings with respect to T-bet + ABCs, since ABC formation depends on IFN-γ and TLR7 signaling in B cells (11).…”

“…These observations, together with another observation that TLR7 expression in B cells is needed for GC appearance in spontaneous autoimmunity (39), are in line with our findings with respect to T-bet + ABCs, since ABC formation depends on IFN-γ and TLR7 signaling in B cells (11). However, the results of some others differ from those reported here in one respect, since some, but not all other studies found that T-bet expression in B cells was not required for spontaneous GC formation (30,31).…”

“…These findings are in line with recent reports indicating that IFN-γR expression in B cells is required for the formation of spontaneous GCs during autoimmunity (30,31) and indicate differential requirements for spontaneous and deliberate GC formation. This finding should be further examined in the future.…”

“…We have established that the T-bet-related transcription factor, EOMES, is not expressed by T-bet-deficient B cells in SLE × T-bet fl/fl × CD19 Cre/WT mice, so it must not act as the replacement for T-bet. It has recently been reported that Bcl-6 expression in B cells is required for the formation of spontaneous GCs and the production of autoreactive antibodies in autoimmune mice (31). Therefore, BCL-6 might be involved in the T-bet-independent development of autoimmune responses.…”

DOCK8 regulates fitness and function of regulatory T cells through modulation of IL-2 signaling

“…Autoantibody titers were measured by ELISA as previously described (59). Briefly, 96-well Immuno plates (Nunc) were precoated overnight at 4°C with calf thymus dsDNA (100 μg/ml; MilliporeSigma, D3664-5X2MG) or Sm/RNP (5 μg/ml; Arotec Diagnostic Limited, ATR01-10).…”