Mdivi-1-Sensitive Mitochondrial Remodeling Contributes to B Cell Immune Synapse Formation and Antigen Presentation.

B cell activation requires the formation of an immune synapse (IS), where coordinated cytoskeletal remodeling and organelle dynamics enable antigen extraction and presentation. While mitochondria are known to regulate cellular metabolism during activation, their role in IS function remains poorly understood. Here, we investigated how mitochondrial dynamics influence antigen processing and presentation in B cells. We show that B cell receptor (BCR) engagement induces rapid phosphorylation of the mitochondrial fission GTPase Drp1 at Ser616. Treatment with mdivi-1, a compound used to perturb Drp1-associated mitochondrial fission that can also affect mitochondrial complex I activity, altered mitochondrial morphology, reduced mitochondrial activity, and decreased their stable accumulation at the synapse. This was accompanied by increased tubulin acetylation, lysosome retention near the MTOC, and reduced delivery to the synaptic membrane. Accordingly, lysosome fusion, antigen extraction, and presentation to T cells were significantly diminished in mdivi-1-treated B cells. Together, our findings suggest that mdivi-1-sensitive mitochondrial fission and activity are associated with mitochondrial positioning, lysosomal trafficking, and exocytosis at the B cell immune synapse, supporting a model in which mitochondrial dynamics contribute to efficient antigen extraction and presentation.