The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor.
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 Igbeta 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.
Treanor
Bebhinn
B
Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Depoil
David
D
Gonzalez-Granja
Aitor
A
Barral
Patricia
P
Weber
Michele
M
Dushek
Omer
O
Bruckbauer
Andreas
A
Batista
Facundo D
FD
D000199:Actins / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D051925:CD79 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology; D007152:Immunologic Capping / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D053778:Thiazolidines / Q000494:pharmacology; D000099149:Ezrin
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D051925:CD79 Antigens; D003598:Cytoskeletal Proteins; D053778:Thiazolidines; D000099149:Ezrin; C037067:latrunculin A