Studies from the 1960's noted that plasma cells had a half-life of only a few days at the early stages of an immune response 1, 2, 3, 4, whereas later studies found that plasma cells could survive for weeks/months 5, 6, 7 or potentially even longer 8. The question of plasma cell longevity and its role in maintaining serum antibody levels has sparked considerable debate over the past 50 years. On the basis of these results, long-lived plasma cells represent a key cell population responsible for long-term antibody production and serological memory. Moreover, BrdU + cells with plasma cell morphology can be detected for 10 years after vaccination/BrdU administration, indicating that plasma cells may persist for a prolonged period of time in the absence of cell division. Here, we present a decade-long study in which we demonstrate site-specific survival of bone marrow-derived plasma cells and durable antibody responses to multiple virus and vaccine antigens in rhesus macaques for years after sustained memory B cell depletion. Clinical studies indicate that antigen-specific antibody responses can be maintained for many years, leading to theories that reactivation/differentiation of memory B cells into plasma cells is required to sustain long-term antibody production. Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear.
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