Enhanced B‐cell activation mediated by TLR4 and BCR crosstalk

Abstract Despite the important role of B lymphocytes as a bridge between the innate and the adaptive immune system, little is known regarding lipopolysaccharide (LPS) recognition, activation of signalling networks or conceivable cooperation between LPS and the B‐cell antigen receptor (BCR). Here, we show that primary B cells can efficiently discriminate between different LPS chemotypes, responding with at least 100‐fold higher sensitivity to rough‐form LPS compared with smooth‐form LPS. Using genetically modified mice, we demonstrate that B lymphocytes recognize all LPS chemotypes via Toll‐like receptor 4 (TLR4). In addition, we dissect the signalling pathways that lead to CD69 upregulation upon TLR4 and BCR activation in primary B cells. Our data suggest that TLR4 and BCR induce CD69 transcription via two distinct sets of signalling molecules, exerting quantitative and qualitative differences in B‐cell activation. Finally, we show that simultaneous stimulation of TLR4 and BCR additively elevates B‐cell activation. In contrast, co‐engagement of TLR4 and BCR by antigen‐coupled LPS synergistically enhances activation of B cells, pointing out attractive targets for signalling crosstalk in B lymphocytes.