There are three possible outcomes when a T cell recognizes a cell bearing a self or foreign antigen. (i) The T cell is not sufficiently signaled and is unaffected. (ii) The T cell is activated. (iii) The T cell is turned off. The differentiation state of the T cell is critical to the outcome. Although both virgin and memory T cells can be activated by antigens presented by "professional" antigen-presenting cells such as dendritic cells, they differ in their responses to B cells. Experienced T cells respond to antigen presented by B cells, whereas virgin T cells are rendered tolerant. These findings may relate to the phenomena of low- and high-zone tolerance, neonatal tolerance, and the beneficial effect of blood transfusions on allograft survival.