The effects of heterologous infections on memory T and B cells.

摘要

Antigenic encounter through infection or vaccination leads to the establishment of memory cells specific for the priming antigen. These cells are maintained for the life of the host and will rapidly assume effector function upon reencounter with the priming agent. The effector mechanisms are mediated via T cells capable of cytokine secretion or cytolytic activity and humoral responses involving constitutive production of antibody. Though much is known about factors contributing to the homeostasis of memory cells, these studies are often conducted with one pathogen. However, in nature a host will encounter many pathogens in its lifetime. Thus a question of fundamental importance is how will a new unrelated infection affect the memory pool.; This thesis explores the effects of unrelated infections upon pre-existing memory T and B cells. Mice were infected with LCMV-Armstrong, VV-WR, or vaccinated with HBV DNA and after memory generation challenged with an heterologous agent. It was found that memory T cells increase slightly at the peak of the immune response to the infected agent, but do not become activated nor decrease expression levels of Bcl-2. Humoral responses were unaffected by VV or Listeria monocytogenes challenge; however, Plasmodium yoelii challenge resulted in massive increases in splenic antibody secreting cells (ASC). Studies to determine the mechanism for the increase showed dependence on CD4+ T cells. Taken together these experiments give detailed analysis of how priming antigens are affected by heterologous infection.; The majority of this antibody is produced in the bone marrow by long-lived plasma cells. Though the majority of antibody secreting cells reside in the bone marrow, antigenic encounter and subsequent germinal center formation occur in the periphery. Although this much is known, it remains poorly understood how plasma cells migrate from germinal centers in secondary lymphoid organs to the bone marrow. In this study, we characterize a new cell population that represents an intermediate stage between germinal center B cells and long-lived plasma cells in the bone marrow. We show these cells to be actively secreting antibody and have many, though not all of the surface characteristics of plasma cells.