Investigating the role of B and T lymphocytes in the course of murine Leishmania Major infection

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.

Grantor dc:publisher.institution

Department of Medicine

Year dc:date.issued

2013

Author dc:creator

• Einhorn, Andrew

Advisor dc:contributor.advisor

• Brombacher, Frank

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/3380

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/3380