The role of the MEK/ERK pathway in regulating cytoskeleton-dependent B cell responses to immobilized and cell-bound antigens

The immune synapse (IS) is a special polarized structure that optimizes the functions of the B cell receptor (BCR), signal transduction and antigen internalization. The B cell IS is formed when B cells bind antigens (Ags) that are displayed on the surface of Ag-presenting cells (APCs), creating an area of contact between the two cells. The binding of the BCR to the Ag on the APC triggers rapid and dynamic reorganization of the BCRs and the cytoskeleton. This allows the cell to spread across the surface of the APC and induces the formation of BCR microclusters throughout the contact site. The microclusters then move centripetally and coalesce into the central supramolecular activation cluster (cSMAC) of an IS. A major signaling pathway initiated by the binding of the BCR to Ags is the Ras/MEK/ERK pathway. Although ERK activity has been implicated in B cell survival and proliferation, the role of ERK in regulating BCR-induced cytoskeletal reorganization, IS formation, and APC-induced BCR signaling has not been investigated. I showed that ERK activity is important for B cells to spread on immobilized Ag. Inhibiting ERK resulted in decreased spreading and altered actin organization. By imaging B cell-APC interactions, I also showed that inhibiting ERK activity impaired IS formation, resulting in decreased APC-induced BCR signaling and delayed cSMAC formation. Thus, ERK may regulate actin-dependent processes that are important for B cell responses to immobilized and APC-bound Ags.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat