Fig. 1. Molecular mechanisms required for the activation of integrin-mediated B-cell adhesion in response to membrane-bound antigens. (A) Prior to antigen stimulation, the `resting' B cell contains BCRs and inactive integrins that are distributed throughout the membrane. Following BCR engagement with antigen on the surface of an antigen-presenting cell (APC) that expresses integrin ligands, crosslinking of BCRs initiates intracellular signalling cascades that result in the inside-out activation of integrins. The molecular details of the intracellular pathways that are shown are based on those identified by Arana et al. and Spaargaren et al. (Arana et al., 2008; Spaargaren et al., 2003). These pathways operate by mechanisms that are dependent on the reorganisation of the cytoskeleton, and allow clustering and activation of integrins as well as the subsequent formation of the immunological synapse (IS). (B) Model of a BCR expressed on the surface of a naive B cell. This BCR comprises a membrane immunoglobulin M (mIgM) in complex with the Ig-Igβ sheath. The mIgM is a heterotetrameter, consisting of two light chains (yellow) and two heavy chains (green) that form distinct Fc and Fab domains. The Fab domains are responsible for binding to antigens, whereas the Fc domain mediates effector functions of antibodies by binding to Fc receptors. The Ig-Igβ sheath allows for transmission of signalling via the BCR through phosphorylation of their immunoreceptor tyrosine-based activation motifs (ITAMs) in their intracellular domains.