Browsing by Author "Einhorn, Andrew"

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    Investigating the role of B and T lymphocytes in the course of murine Leishmania Major infection
    (2013) Einhorn, Andrew; Brombacher, Frank
    This thesis is composed of two parts. The first is an investigation of the role of B-effector cells in the course of murine Leishmania Major (L. major). The second is a bioinformatic analysis of microarray slides of activated CD4 T-cells from L. major infected BALB/c and C57BL/6 mice in order to investigate the genetic determinants of their divergent disease phenotypes. Overall this thesis is an investigation of the role of B-and T-lymphocytes during the course of L. major infection in mice. B-cells are not traditionally thought to play a role in the pathogenesis of Leishmania major infection. It is well documented that T-helper 1(Th1) and T-helper 2 (Th2) responses lead to resistance and susceptiblity to L. major respectively. Recent studies have now shown that B-cells are capable to producing key T-cell differentiating cytokines such as IL-4 and IFN-γ. More specifically, two new B-cell populations have been identified: B effector 1 (Be1) and B effector 2 (Be2) cells, which produce IFN-γ and IL-4 respectively. Using mice lacking the IL-4Rα on B-cells, and thus incapble of producing Be2 cells, we investigate the contribution of Be2 cells to BALB/c susceptibility. We confirm that the delection of the IL-4Rα on B-cells renders the previously susceptible BALB/c mice resistant to L. major strain LV39 and further confirm the phenotype using the more the virulent IL81 strain. We demonstrate that mice lacking Be2 cells exhibit a dimished Th2 response and an enhanced Th1 response, suggesting that B-cells, in addition to their role in antibody production, may also play a role in shaping T-helper responses in vivo. In the case of L.major, this provides evidence for a novel link between B cells and the cellular immune response.