Plasma cells and the persistence of antibody-mediated immunity

Abstract

Long-term immunity depends on the sustained maintenance of antigen-specific antibodies. How protective antibody levels can be maintained long-term remains incompletely understood. Antibody titres against pathogens such as measles remain for life, whereas titres against SARS-CoV-2 usually wane within months. B-cell depletion studies in humans and mice demonstrate that antibody titres remain relatively stable even in the absence of naïve and memory B cells, suggesting a central role for long-lived plasma cells (LLPCs). However, LLPCs are rare and may depend on specialised survival niches. In addition, declining antibody titres at the start of B-cell depletion therapy indicate that short-lived plasma cells also contribute to humoral maintenance. The factors determining the longevity of antibody responses remain unclear, partly due to challenges in identifying LLPCs and inconsistencies in their definition across studies. Since LLPCs are thought to be mostly class-switched cells, displaying high antigen affinity, durable germinal centre (GC) reactions are considered essential for LLPC formation. However, some studies indicate that GC-independent responses can also last long-term. The duration of antibody responses may depend on a combination of short- and long-lived plasma cells that varies between antigens, as well as the strength of the response. Future research should prioritise longitudinal, antigen-specific analyses that integrate both serological and cellular data. In particular, B-cell depletion studies that simultaneously track antibody titres and plasma cell populations within the same individuals would provide valuable insights into the dynamics of humoral memory.