title: Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling.
abstract: Receptor organization and dynamics at the cell membrane are important factors of signal transduction regulation. Using super-resolution microscopy and single-particle tracking, we show how the negative coreceptor CD22 works with the cortical cytoskeleton in restraining BCR signalling. In naïve B cells, we found endogenous CD22 to be highly mobile and organized into nanodomains. The landscape of CD22 and its lateral diffusion were perturbed either in the absence of CD45 or when the CD22 lectin domain was mutated. To understand how a relatively low number of CD22 molecules can keep BCR signalling in check, we generated Brownian dynamic simulations and supported them with ex vivo experiments. This combined approach suggests that the inhibitory function of CD22 is influenced by its nanoscale organization and is ensured by its fast diffusion enabling a "global BCR surveillance" at the plasma membrane.
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gasparrini
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Christoph
authors.initials: C
authors.lastname: Feest
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruckbauer
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Pieta K
authors.initials: PK
authors.lastname: Mattila
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Müller
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Dennis
authors.initials: D
authors.lastname: Bray
authors.affiliation: Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, UK facundo.batista@crick.ac.uk.
authors.forename: Facundo D
authors.initials: FD
authors.lastname: Batista
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497868:Cd22 protein, mouse; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2
keywords: B‐cell receptor signalling; glycoprotein CD45; membrane dynamics; siglec CD22; super‐resolution microscopy