T-bet supports differentiation of B-effectors into antibody secreting cells (P1316)

Abstract

Abstract Memory B cells (Bmem) and long-lived plasma cells (LLPC) arise from germinal center B cells (GCB). The transcription factor Bcl6 is required for GCB cell survival and the development of Bmem. By contrast, Bcl6 inhibits LLPC development by repressing the transcription factor Blimp1. To date, it is not clear how these opposing transcription factors are regulated in GCB cells. In T cells, T-bet modulates the balance between Blimp1 and Bcl6 and controls their subsequent differentiation into memory and effector cells. We recently defined a B-cell subset, referred to as B-effector 1 cells (Be-1 cells), that express high levels of T-bet and secrete IFNγ. We showed that IFNγ or T-bet deficient Be-1 cells inefficiently seed the LLPC compartment, leading us to suspect that the Be-1 cells may be precursors to LLPCs and Bmem. We hypothesized that T-bet expression by Be-1 cells promotes cytokine production and supports their differential development into antibody secreting cells (ASCs). We found that the IFNγ producing CXCR3+ CCR6+ Be-1 cells expressed higher levels of Bcl6 and T-bet but lower levels of Blimp1 and XBP1 compared to the non-Be-1 cells. T-bet-/- Be-1 cells expressed lower levels of Blimp1 and XBP1, but higher levels of Bcl6. Further, T-bet-/- and IFNγ-/- Be-1 cells had attenuated IFNγ production and antibody secretion. These results support a role for T-bet in determining Blimp1 and Bcl6 levels in B-effectors and modulating their development into ASCs rather than Bmem cells.