TLR9-ligation in naive B cells activates NF-κB and PKM2 tetramer shift for glycolytic reprogramming and TNF expression

The innate-like function of B cell is dependent on pattern recognition receptors, such as Toll-like receptors (TLR). TLR ligation and activation of downstream signaling pathways drives metabolic changes in cells and promotes effector functions (e.g., cytokine secretion). However, the immunometabolic profile of B cells during the initial recognition of pathogen associated molecular patterns via Toll-like receptor 9 in the innate immune response is limited. TLR9-activation in B cells by CpG elicits an increased glycolytic response mediated by NF-κB, which in and of itself is a strong mediator of metabolism and immune function. However, we further define the role of NF-kB mediated metabolic switch to facilitate a temporal shift in PKM2 tetramerization status sensitive to IKK inhibition that induces B cell expression of TNF (Figure 1).