B‐cell receptor: from resting state to activate

Summary B‐cell activation is triggered by the binding of antigen to the B‐cell receptor (BCR). The early molecular events triggered by BCR binding of ligand have been well‐characterized both biochemically and using optical microscopy techniques to visualize B‐cell activation as it happens. However, we understand much less about the BCR before activation. For this reason, this review will address recent advances in our view of the structure, organization and dynamics of the resting, unstimulated BCR. These parameters have important implications for our understanding of the initiation of B‐cell activation and will be discussed in the context of current models for BCR activation. These models include the conformation‐induced oligomerization model, in which binding of antigen to monomeric BCR induces a pulling or twisting force causing conformational unmasking of a clustering interface in the Cμ4 domain. Conversely, the dissociation activation model proposes that BCRs exist in auto‐inhibitory oligomers on the resting B‐cell surface and binding of antigen promotes the dissociation of the BCR oligomer exposing phosphorylation residues within Igα/Igβ. Finally, the collision coupling model suggests that BCR are segregated from activating co‐receptors or kinases and activation is associated with changes in BCR mobility on the cell surface, which allows for the functional interaction of these elements.