Analysis of membrane exchange between lymphocytes release_ykgqne2jxbd37afzj2vfwy2dzq

Abstract

Membrane transfer is the cell-to-cell contact dependent exchange of plasma membrane and surface molecules between cells. It has been described for a wide range of immune cells, nevertheless the molecular mechanisms mediating this exchange remain unclear. The studies outlined in this Thesis provide new insights and a better understanding of the transfer process. Previous studies in my supervisor's laboratory showed that activated antigen- specific B cells and T cells readily donate their antigen-specific receptors to neighbouring lymphocytes of an unrelated specificity via plasma membrane exchange. Results obtained in this Thesis confirmed and further characterised several properties of antigen receptor transfer as well as suggesting new potential mediators of membrane exchange. The results in Chapter 3 detail important properties of membrane exchange between B cells, and based on these unique features propose a molecular mechanism for this process. It was confirmed that B cells require appropriate activation conditions in order to donate membranes and cell surface proteins, with naïve B cells being much less capable of transfer. Additionally, it was confirmed that activated B cells are capable of transferring membranes and surface proteins at 4oC, thus excluding many of the currently proposed energy dependent mechanisms. Chapter 3 describes the investigation of an energy independent mechanism of exchange involving cell penetrating peptide (CPP) motifs. The results obtained demonstrate that analogous to transfer between B cells, CPPs are up to 40-fold more efficiently taken up by activated, rather than naïve, B cells and that this uptake occurs at both 37oC and 4oC. These data suggest that receptors involved in the initiation of membrane transfer may contain CPP motifs important in facilitating this process. Chapter 4 describes attempts to identify the molecular basis of membrane transfer via a comparative gene expression analysis. This study took advantage of the finding that B cells require appropriate activatio [...]
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