Vaccination acts by inducing the clonal expansion and differentiation of antigen specific lymphocytes that persist for a lifetime as memory cells. Memory cells mediate two functions: they confer immediate protection in peripheral tissue and mount recall responses in secondary lymphoid organs. These functions are carried out by distinct cell types. In the B lymphocyte system protective memory is mediated by plasma cells that secrete antibodies, while reactive memory is mediated by memory B cells that are present in lymphoid organs and proliferate and differentiate to plasma cells in response to secondary antigenic stimulation. A similar division of labor has been recently defined for T lymphocytes. Protective memory is mediated by effector memory T cells (TEM) that home to inflamed peripheral tissues and display immediate effector function, while reactive memory is mediated by a distinct subset of central memory T cells (TCM) that retain lymph node homing receptors and high proliferative capacity in response to antigenic challenge.
I will review the experimental evidence supporting a "stem cell model" of immunological memory. Memory B cells and central memory T cells are intermediates of a progressive differentiation process which have acquired the capacity to proliferate and differentiate in response to polyclonal stimuli such as cytokines, microbial products or bystander T cell help. While self-renewing, memory B cells and central memory T cells continuously spill out plasma cells and effector T cells, thus replenishing those that turn over. Furthermore I will describe in detail the mechanisms that sustain serum antibody levels following vaccination and discuss the implications of these findings for vaccine design.
This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
- Copyright © 2003 by Antonio Lanzavecchia