Characterizing Mechanical Forces during B Cell Responses

Abstract

B cells are components of the adaptive immune response that produce high-affinity antibodies that neutralize and provide immunity against infections. Their responses are initiated when the B cell receptor (BCR) binds foreign antigen, triggering intracellular signaling that leads to B cell activation. Current evidence suggests that to elicit a full immune response involving development into high-affinity memory and plasma cells, B cells need to acquire the antigen from immune synapses with antigen presenting cells, and then internalize, process and present it to receive T cell help. Recent studies from our group suggest that B cells use contractile force to physically extract antigen from the presenting membrane prior to endocytosis. In addition, it was shown that pulling on the BCR-antigen bond results in discrimination between high- and low-affinity interactions. This suggests that B cells mechanically test the strength of BCR-antigen bonds to actively regulate affinity discrimination, a process that is important for the efficient development of high-affinity antibodies. To characterize force generation in the B cell synapse, we combine live-cell imaging with molecular force sensors. For the first time, we resolve the spatiotemporal dynamics and magnitude of mechanical forces in the B cell synapse, giving us insight into how B cells use mechanical forces to actively regulate their responses to antigen binding.