Non-muscle myosin II-B enhances T cell mechanosensing and is induced during activation to promote cell migration and proliferation

NM2-B is a molecular motor specialized in sustained tension maintenance across the actomyosin cytoskeleton in mesenchymal and neural cells, yet its specific roles in immune cells remain poorly understood. Here, we show that NM2-B confines actin protrusion and enables the spatial segregation of activation mediators in a leukemic model of antigenic presentation. In primary human T cells, various activating signals increase the expression of the NM2-B heavy chain. Activation-induced NM2-B is required for morphological polarization, chemotactic migration and proliferation in response to antigenic and mitogenic signals, despite accounting for less than 5% of total cellular NM2. Conversely, partial depletion of NM2-A, which accounts for the majority (> 95%) of total NM2 in activated T cells, does not significantly affect these processes. Our work demonstrates that NM2-B induction enhances mechanosensing and supports the proliferative demands of T cell activation, establishing this minor isoform as a previously unrecognized regulator of T cell activation, polarization and proliferation.