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Antigen presentation by B cells is regulated by intracellular processes relying on conserved regulators of actin cytoskeleton and cell polarity.Defects in actin cytoskeleton regulators cause severe defects in B cell functionand impair humoral immune responses.B cells deficient in actin cytoskeleton regulators are impaired in interacting with T cells at the B–T border and seeding GC responses.B cells are an integral part of the adaptive immune system. During an immune response, the actin cytoskeleton plays a central role in regulating B cell antigen uptake, polarization and presentation as well as B cell migration and interaction with T cells. Genetic defects affecting actin regulators can result in reduced B cell activation, limited antibody production and hence cause disease. In this review, we discuss molecular mechanisms of actin regulation and their involvement in antigen polarisation and presentation, as well as their role in influencing interactions between B and T cells. Improved understanding of these mechanisms is necessary for the development of new therapeutic options modulating humoral immune responses.