title: The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling.
abstract: A key role is emerging for the cytoskeleton in coordinating receptor signaling, although the underlying molecular requirements remain unclear. Here we show that cytoskeleton disruption triggered signaling requiring not only the B cell receptor (BCR), but also the coreceptor CD19 and tetraspanin CD81, thus providing a mechanism for signal amplification upon surface-bound antigen stimulation. By using superresolution microscopy, we demonstrated that endogenous IgM, IgD, and CD19 exhibited distinct nanoscale organization within the plasma membrane of primary B cells. Upon stimulation, we detect a local convergence of receptors, although their global organization was not dramatically altered. Thus, we postulate that cytoskeleton reorganization releases BCR nanoclusters, which can interact with CD19 held in place by the tetraspanin network. These results not only suggest that receptor compartmentalization regulates antigen-induced activation but also imply a potential role for CD19 in mediating ligand-independent "tonic" BCR signaling necessary for B cell survival.
authors.affiliation: Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Pieta K
authors.initials: PK
authors.lastname: Mattila
authors.forename: Christoph
authors.initials: C
authors.lastname: Feest
authors.forename: David
authors.initials: D
authors.lastname: Depoil
authors.forename: Bebhinn
authors.initials: B
authors.lastname: Treanor
authors.forename: Beatriz
authors.initials: B
authors.lastname: Montaner
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Otipoby
authors.forename: Robert
authors.initials: R
authors.lastname: Carter
authors.forename: Louis B
authors.initials: LB
authors.lastname: Justement
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruckbauer
authors.forename: Facundo D
authors.initials: FD
authors.lastname: Batista
mesh_terms: D000199:Actins / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015151:Immunoblotting; D007072:Immunoglobulin D / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018448:Models, Immunological; D049329:Nanostructures; D011485:Protein Binding / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D060225:Tetraspanin 28 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000199:Actins; D018941:Antigens, CD19; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D060225:Tetraspanin 28