B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

• Published in: eLife Vol. 3; p. e02069
• Main Authors: Kläsener, Kathrin, Maity, Palash C, Hobeika, Elias, Yang, Jianying, Reth, Michael
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 24.06.2014; eLife Sciences Publications, Ltd
• Subjects: Animals; Annealing; Antigens; B cell antigen receptor; B-cell receptor; B-Lymphocytes - metabolism; CD19 antigen; Cell activation; Cell Line; Conformation; Cytoskeleton; Deoxyribonucleic acid; Dimerization; DNA; Exports; Flow cytometry; Humans; Immunoglobulin D; Immunoglobulin M; Immunoglobulins; Immunology; inside-out signaling; Lymphocyte Activation; Lymphocytes B; Mice; nanoscale receptor organization; Plasmids; Proteins; Receptor density; Receptors, Antigen, B-Cell - metabolism; Signal Transduction; Software; Syk protein; nanoscale receptor organization; B cell antigen receptor; inside-out signaling
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.02069

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.