Quantitative Investigation Of Mechanosensing In B Cell Activation

B cell activation is triggered by specific binding events between the B cell receptor (BCR) and antigens presented by antigen-presenting cells (APCs). B cell activation is well-characterised biochemically, but the role of physical factors is poorly understood. It has been shown in vitro that for a given antigen density, B cell triggering is enhanced on stiff substrates relative to softer substrates. When the substrate rigidity is kept constant, B cell triggering positively correlates with antigen affinity up to 50 µM−1, above which B cells respond maximally independent of antigen affinity. Additionally, the minimum antigen density required to induce a B cell response inversely correlates with antigen affinity. B cells can sense these myriad physical parameters through information encoded in BCR-antigen bonds, although the mechanisms are unclear. Here, we aim to understand how B cell responses to antigen are influenced by physical factors in the immune synapse. We are using high-resolution fluorescence microscopy and quantitative image analysis to systematically investigate how antigen affinity, antigen density and substrate stiffness influence B cell activation. This work will help build a quantitative understanding of B cell mechanosensing, which is important for the rational design of new vaccines and immunotherapies.