The Membrane Skeleton Controls Diffusion Dynamics and Signaling through the B Cell Receptor

• Published in: Immunity (Cambridge, Mass.) Vol. 32; no. 2; pp. 187 - 199
• Main Authors: Treanor, Bebhinn, Depoil, David, Gonzalez-Granja, Aitor, Barral, Patricia, Weber, Michele, Dushek, Omer, Bruckbauer, Andreas, Batista, Facundo D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.02.2010; Elsevier Limited; Cell Press
• Subjects: Actins - immunology; Actins - metabolism; Animals; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Behavior; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cameras; CD79 Antigens - genetics; CD79 Antigens - immunology; CD79 Antigens - metabolism; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - immunology; Cell Membrane - metabolism; Cytoskeletal Proteins - immunology; Cytoskeletal Proteins - metabolism; Cytoskeleton; Cytoskeleton - drug effects; Cytoskeleton - immunology; Diffusion; Immunologic Capping - drug effects; Immunologic Capping - genetics; Immunologic Capping - immunology; Kinases; Medical research; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Microscopy, Fluorescence; MOLIMMUNO; Phosphorylation; Plasma; Protein Binding; Protein Engineering; Protein Structure, Tertiary - genetics; Proteins; Rodents; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - immunology; Studies; Thiazolidines - pharmacology; MOLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2009.12.005

Early events of B cell activation after B cell receptor (BCR) triggering have been well characterized. However, little is known about the steady state of the BCR on the cell surface. Here, we simultaneously visualize single BCR particles and components of the membrane skeleton. We show that an ezrin- and actin-defined network influenced steady-state BCR diffusion by creating boundaries that restrict BCR diffusion. We identified the intracellular domain of Igβ as important in mediating this restriction in diffusion. Importantly, alteration of this network was sufficient to induce robust intracellular signaling and concomitant increase in BCR mobility. Moreover, by using B cells deficient in key signaling molecules, we show that this signaling was most probably initiated by the BCR. Thus, our results suggest the membrane skeleton plays a crucial function in controlling BCR dynamics and thereby signaling, in a way that could be important for understanding tonic signaling necessary for B cell development and survival. ► An ezrin- and actin-defined network creates barriers to restrict BCR diffusion ► The intracellular domain of Igβ mediates restricted BCR diffusion ► Alteration of the actin network is sufficient to induce intracellular signaling ► Signaling induced by altering the actin network is mediated by BCR