Activated B cells develop high cytoskeletal activity and actively engage T cells in a multifocal manner. OVA-loaded naive B cells were activated for 72 hours in the presence of DO11.10 T cells, purified, reloaded with OVA, and embedded with fresh DO11.10 T cells in 3-D collagen. (A) Activated B cells (green) display effective migration and a prominent cytoskeletal activity (Supplemental Movie 9) 30 minutes after culture set-up. (B) The formation of a contact to a DO11.10 T cell (T) involves active grabbing by B-cell membrane protrusions (white arrowheads), the movement of the B cell around the T-cell body, and its subsequent dragging by the motile B cell in its direction of movement (white arrow, and Supplemental Movie 10) 30 minutes after culture set-up. (C) SEM of DO11.10 T cells in contact with an activated B cell. The activated B cell is able to contact 4 T cells simultaneously, thereby making intense multifocal contacts to the T cells by the generation of membrane protrusions. Scale bar: 10 μm. White numbers indicate minutes of real time.