Adaptation of humoral memory

Abstract

Immunological memory, as provided by antibodies, depends on the continued presence of antibody-secreting cells, such as long-lived plasma cells of the bone marrow. Survival niches for these memory plasma cells are limited in number. In an established immune system, acquisition of new plasma cells, generated in response to recent pathogenic challenges, requires elimination of old memory plasma cells. Here, we review the adaptation of plasma cell memory to new pathogens. This adaptation is dependent upon the influx of plasmablasts, generated in a secondary systemic immune reaction, into the pool of memory plasma cells, the efficiency of competition of new plasmablasts with old plasma cells, and the frequency of infection with novel pathogens. To maintain old plasma cells at frequencies high enough to provide protection and to accommodate as many specificities as possible, an optimal influx rate per infection exists. This optimal rate is approximately three times higher than the minimal number of plasma cells providing protection. Influx rates of plasmablasts generated by vaccination approximately match this optimum level. Furthermore, the observed stability of serum concentrations of vaccine-specific antibodies implies that the influxing plasmablasts mobilize a similar number of plasma cells and that competitive infectious challenges are not more frequent than once per month.