Differential regulation of TLR4 expression in human B cells and monocytes

Toll-like receptor 4 (TLR4) is an innate immune receptor that is constitutively and inducibly activated in monocytes Although TLR4 is expressed at very low levels on human B cells from healthy individuals recent reports showed that TLR4 expression and function is elevated in B cells from inflammatory disease patients New data showed that TLR4 expression on B cells is Increased upon stimulation through surface Ig mu and CD40 in combination with IL-4 In contrast monocyte stimulation through CD40 and IL-4 receptors decreased TLR4 surface expression Analysis of molecular signatures of TLR4 activation in stimulated B cells suggested that TLR4 is regulated by different mechanisms in B cells compared to monocytes PU 1 and interferon regulatory factor association with the TLR4 promoter are sufficient for TLR4 transcription but are not sufficient for surface TLR4 expression on B cells In contrast the PU 1/IRF combination is sufficient for surface TLR4 expression on monocytes These data identify mechanisms that can activate B cell TLR4 expression in inflammatory disease patients and demonstrate that B cells have additional layers of TLR4 regulation absent in monocytes (C) 2010 Elsevier Ltd All rights reserved