Enhanced B-cell activation mediated by TLR4 and BCR crosstalk.
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.
Minguet
Susana
S
Molecular Immunology, Institute of Biology III, University of Freiburg and Max Planck-Institute for Immunobiology, Freiburg, Germany. sminguet@gmail.com
Dopfer
Elaine P
EP
Pollmer
Careen
C
Freudenberg
Marina A
MA
Galanos
Chris
C
Reth
Michael
M
Huber
Michael
M
Schamel
Wolfgang W
WW
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D051197:Toll-Like Receptor 4; D000099192:CD69 Antigens; C493487:Tlr4 protein, mouse