Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement.

ABSTRACT: B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity, a process known as affinity discrimination. We use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial engagement. We find that if B-cell receptors become signaling-capable immediately upon antigen binding, which results in decreasing serial engagement as affinity increases, then increasing affinity can lead to weaker signaling. Rather, antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable, a process similar to kinetic proofreading. This process overcomes the loss in serial engagement due to increasing antigen affinity, and replicates the monotonic increase i

SUBMITTER: Tsourkas PK 

PROVIDER: S-EPMC3756518 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature