MTOR activity is necessary for cytokine-mediated TBET expression in TLR-stimulated B cells

Abstract

Abstract A recently described subset of B cells – called age associated B cells (ABCs) – is characterized by the increased expression of TBET. While known to be particularly relevant in the settings of aging and autoimmunity, the cell intrinsic signaling pathways leading to the development of the ABC phenotype are not well-characterized. Since the mTOR pathway is a known regulator of TBET expression in other cell types, we examined its role in B cells stimulated with TLR agonists. Our findings indicate that TLR9 (CpG) or TLR7 (Cl097) ligands alone activate mTOR, as evidenced by S6 phosphorylation, but do not yield robust TBET upregulation without concomitant cytokine stimulation. Indeed, IFNγ and IL-21 induced TBET expression is lost in response to rapamycin (mTOR inhibitor) treatment. This indicates that mTOR activity is necessary but not sufficient for TBET expression. The implication that mTOR could be a node for integration of signals downstream of TLR and cytokines to regulate TBET expression in B cells merits further investigation, and might provide novel mechanistic insights into various B cell differentiation programs.