Staying alive: regulation of plasma cell survival

On describing the catastrophic effect of the plague during the Peloponnesian War, Greek historian Thucydides (c ∼450 BC) made the prescient observation that the “same man was never attacked twice – never at least fatally”. This is probably the first description of the mammalian immune systems’ remarkable ability to elicit a pathogen-specific response that potentially protects the host for its lifetime. This protection is largely mediated by plasma cells (PCs) that produce copious quantities of antibodies for extended periods of time, even after pathogen clearance. Here, I review the requirements for PC longevity in mice and humans, in particular the roles of survival niches in bone marrow and other tissues, and the “dialogue” between PCs and other cells that are crucial for long-lived humoral immunity.