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.
See also: D Depoil & ML Dustin (February 2016)
The inhibitory activity of CD22 on BCR signalling relies on its distribution into nanoclusters and high lateral mobility as shown by super‐resolution microscopy and in silico simulations. These properties are CD45 dependent and enable CD22 to efficiently scan the B‐cell membrane and, jointly with the actin cytoskeleton, restrain BCR signalling.
The alteration of the actin cytoskeleton activates both positive and negative signalling molecules similarly to BCR ligand‐dependent stimulation.
The inhibitory coreceptor CD22 is highly mobile and organized into nanodomains on the membrane of naïve B cells.
The binding of CD22 to sialic acid and CD45 controls CD22 mobility and organization at the plasma membrane.
CD22 organization and fast lateral mobility provide a means of restraining BCR tonic and ligand‐dependent signalling.
The EMBO Journal (2016) 35: 258–280
- Received September 8, 2015.
- Revision received November 4, 2015.
- Accepted November 9, 2015.
- © 2015 The Authors
Subscribers, please sign in with your username and password.