In the steady state, CD22 dynamics and nanoclustering are regulated by CD45. Sialylated CD45 works as a spacer between mobile molecules of CD22 displaying high amount of sialic acid. This organization limits the extent of active CD22 (red tails, side view) and restrains the proximity of CD22 to the BCR (long arrow, side view). This equilibrium allows a low level of basal signalling required for B‐cell survival.
When CD45 is absent, the tendency of CD22 to form self‐interactions via sialic acid binding increases together with CD22 nanocluster size and inhibitory activity. Bigger clusters of hyperactive CD22, no longer trapped by CD45, can access the BCR more easily (short arrow, side view) restraining the signalling.
The inability of CD22 to bind the sialic acid (Cd22
R130E) on either CD45 or neighbouring CD22 molecules decreases the size of CD22 nanoclusters with a concomitant increase of CD22 lateral mobility (dashed arrows, side view and top view) and phosphorylation. In this situation, CD22 is able to explore a larger area and access more BCRs (short arrow, side view), thus leading to a higher signal inhibition.
