Abstract
T cell receptor (TCR) and B cell receptor (BCR) stimulation by antigen presented on an antigen-presenting cell (APC) induces the formation of the immune synapse (IS), the convergence of secretory vesicles from T and B lymphocytes toward the centrosome, and the polarization of the centrosome to the immune synapse. Immune synapse formation is associated with an initial increase in cortical F-actin at the synapse, followed by a decrease in F-actin density at the central region of the immune synapse, which contains the secretory domain. These reversible, actin cytoskeleton reorganization processes occur during lytic granule degranulation in cytotoxic T lymphocytes (CTL) and cytokine-containing vesicle secretion in T-helper (Th) lymphocytes. Recent evidences obtained in T and B lymphocytes forming synapses show that F-actin reorganization also occurs at the centrosomal area. F-actin reduction at the centrosomal area appears to be involved in centrosome polarization. In this review we deal with the biological significance of both cortical and centrosomal area F-actin reorganization and some of the derived biological consequences.
Highlights
T and B lymphocyte activation by antigen-presenting cells (APC) takes place at a specialized cell to cell interface called the immunological synapse (IS)
T cell receptor (TCR) and B cell receptor (BCR) stimulation by antigen presented by APC, together with accessory molecules interaction with their ligands on the APC, induces IS formation, convergence of T and B lymphocyte secretory vesicles toward the centrosome and, almost simultaneously, centrosome polarization to the IS (Huse, 2012; de la Roche et al, 2016)
We have shown that filamentous actin (F-actin) clearing at the central supramolecular activation complex (SMAC) (cSMAC) and centrosomal area F-actin depletion, respectively, mediated by protein kinase C δ isoform (PKCδ)-dependent phosphorylation of FMNL1β or paxillin, are associated with centrosome/multivesicular bodies (MVB) polarization and exosome secretion in CD4+ Jurkat T lymphocytes forming IS (Herranz et al, 2019; Bello-Gamboa et al, 2020) (Figure 1B)
Summary
T and B lymphocyte activation by antigen-presenting cells (APC) takes place at a specialized cell to cell interface called the immunological synapse (IS). It has been shown that PKCδ-dependent F-actin clearing at the cSMAC and PKCδ-dependent phosphorylation of formin FMNL1β at the IS, are involved in centrosome/MVB polarization leading to exosome secretion in CD4+ Jurkat T lymphocytes forming IS (Herranz et al, 2019; Bello-Gamboa et al, 2020).
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