Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Antibody persistence frequently determines the longevity of immunity, yet the mechanisms that set antibody-producing plasma cell turnover rates are unestablished. While it is proposed that new plasma cells displace existing ones in competition for specialised survival niches, it is also possible that the spontaneous loss of existing plasma cells frees niches thereby creating opportunities for recruitment, possibilities with quite different implications for maximising antibody production and persistence. Here, using a genetic reporter to timestamp plasma cells, we define the distribution, phenotype, transcriptional program and population structure of long-lived plasma cells and calculate turnover dynamics. We show that the attributes of longevity are acquired and that turnover of long-lived plasma cells at homeostasis is unaffected by the absence of B cells, indicating that the mechanism of turnover is independent of competition. We propose that understanding plasma cell population dynamics may allow their manipulation to achieve specific outcomes. BLTcre.mcl1fl/+ reporter mice were given tamoxifen to trigger the expression of a reporter human CD4 gene. Whole transcriptome RNA sequencing of human CD4+ and human CD4- plasma cells sorted from BLTcre.mcl1fl/+ reporter mice 60 days and 270 days after tamoxifen treatment