B Cells are Activated via a Nanoporous Interface that Stabilizes Microvilli and Engages Mechanosensitive Ion Channels

B cell activation typically involves binding of presented antigen by the B cell receptor. Ensuing intracellular signaling with Ca 2+ mobilization, cytoskeletal remodeling, and transcriptional changes culminates in an appropriate B cell response. Recently, our group developed an antigen receptor‐independent, purely mechanobiological activation platform for T cells. Nanotopological stimulation by exposure to a porous membrane, resulted in robust T cell activation. Whether and how B cells are activated by this substrate on a mechanistic level is presently unknown. Here we report that nanoporous stimulation indeed results in B cell activation, where B cells extended nanopore penetrating microvilli and exhibited activation hallmarks including intracellular Ca 2+ spikes, phosphorylation of signaling components, and cell surface expression of the activation marker cluster of differentiation (CD) 69, thus recapitulating T cell behavior. This is at least partially mediated by mechanosensitive cation channels, as determined by pharmacology. In summary, our findings demonstrate that B cells are amenable to antigen receptor‐independent activation via nanopores, expanding our knowledge on B cell activation mechanisms.