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B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk
Kathrin Kläsener1, Palash C Maity1, Elias Hobeika1
1BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany.
Abstract:
Binding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10-20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation.DOI: http://dx.doi.org/10.7554/eLife.02069.001.
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