The mechanics of B cell activation in the immune synapse
Adaptive immune responses begin with the activation of B cells, mediated by specific binding of their unique B cell receptors (BCRs) to antigens presented on the surfaces of antigen-presenting cells (APCs). Interactions between BCRs and surface-anchored antigens in B cell-APC contacts, called immune synapses, provide signals to the B cell that direct it to survive, proliferate, and generate antibodies to eliminate the antigen, or to die. This mechanism underpins the rapid evolution of high-affinity antibodies to combat the infection. Thus, the activation decisions that B cells make in the immune synapse impact the scope of the immune response. In this talk, I will discuss our efforts to understand how B cells detect and discriminate antigens, and how physical properties of the APC surface impact the sensitivity and specificity of this process. We do this using high-resolution fluorescence microscopy to directly observe B cell activation events in combination with DNA nanotechnology to control physical properties of the immune synapse, such as molecular spatial arrangements and mechanical tension. These experiments yield molecular insight into B cell reactions to antigens during an immune response.