Changes in splenic microarchitecture and B cell responses in acute and chronic Plasmodium chabaudi chabaudi (as) infection in mice
This thesis investigates the order and timing of changes in the splenic microarchitecture and the lifespan and kinetics of B cells and plasma cells during primary acute P.chabaudi infection, and the length of chronic P.chabaudi infection. Infected red blood cells can be seen in the spleen as soon as 1 hour post infection, alterations in the splenic microarchitecture begin at day 5 post-infection with the movement of dendritic cells and the merging of B and T cell zones. Macrophages and B cells of the marginal zone are lost from this location by day 10 post-infection, however there is no alteration in the location of red pulp macrophages. Large numbers of plasma cells can be seen in the spleen from day 8 post-infection, when they switch from IgM* to IgG+. The adhesion molecule MAdCAM-1 is more widely expressed, although not on reticular fibroblasts or red pulp endothelial cells. The significance of these alterations, and the mechanisms responsible, are discussed. Chronic, subpatent parasitaemia in P.chabaudi infection is cleared by 3 months post-infection in C57BL/6 mice, and 2 months in BALB/c mice. Most changes in B cell and plasma cell formation occur during the acute infection, and are resolved by 6 weeks post-infection. The number of B cells in the bone marrow is reduced, and plasma cell production in the spleen is high during acute infection. Plasma cell migration to the bone marrow is consistently lower in infected mice than naive mice. The majority of B cells and plasma cells produced throughout the acute and chronic infection are short-lived, with little evidence of production of long-lived cells. B cell and plasma cell formation is still elevated at 12 weeks post-infection, indicating that B cells and plasma cells during this period may be maintained by continuous turnover rather than production of long-lived cells.