What persuades a memory lymphocyte to stick around for years after an infection has been cleared? For B cells, the explanations have been that either antigens persist somehow or that some B cells develop into long-lived antibody-secreting plasma cells that need no stimulation. Bernasconi et al. provide evidence for an intermediate mechanism in which nonspecific stimuli--not limited to antigens from any one pathogen--spur B cells into continued antibody production. In culture, human memory, but not naïve, B cells divided strongly in response to CpG sequences of DNA, which are powerful signals to innate immune cells. The T cell cytokine interleukin-15 evoked the same response, and like CpG, could induce some B cells to become plasma cells. Frequencies of antigen-specific plasma B cells and levels of circulating antibody in individuals over a decade after vaccination agreed with predictions made from these experiments. N. L. Bernasconi, E. Traggiai, A. Lanzavecchia, Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298 , 2199-2202 (2002). [Abstract] [Full Text]