Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Antibodies produced by antibody-secreting plasma cells (ASCs) underlie multiple forms of long-lasting im-munity. Here we examined the mechanisms regulating ASC turnover and persistence using a genetic reporter to time-stamp ASCs. This approach revealed ASC lifespans as heterogeneous and falling on a continuum, with only a small fraction surviving for >60 days. ASC longevity past 60 days was independent of isotype but correlated with a phenotype that developed progressively and ultimately associated with an underlying long-lived ASC (LL ASC)-enriched transcriptional program. While some of the differences between LL ASCs and other ASCs appeared to be acquired with age, other features were shared with some younger ASCs, such as high CD138 and CD93. Turnover was unaffected by altered ASC production, arguing against competition for niches as a major driver of turnover. Thus, ASC turnover is set by intrinsic lifespan limits, with steady-state population dynamics governed by niche vacancy rather than displacement.

Automated summary

By using a genetic reporter to track ASCs, we have investigated the mechanisms regulating ASC lifespan and persistence. We found that the lifespan of ASCs is heterogeneous, with only a small fraction surviving for more than 60 days. ASC longevity beyond 60 days is associated with a transcriptional program enriched in long-lived ASCs. Thus, ASC turnover is primarily governed by intrinsic lifespan limits, with population dynamics influenced by niche vacancy rather than displacement.