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.

抗体持久性往往决定免疫存续时长，但调控抗体生成浆细胞（plasma cell）更新速率的具体机制仍未阐明。尽管有假说提出，新生浆细胞可通过竞争专属生存龛（survival niche）取代已存在的浆细胞，但也存在另一种可能性：已存在的浆细胞自发消亡会释放生存龛，从而为浆细胞招募创造空间——这两种可能性对抗体生成与持久性的最大化有着截然不同的影响。本研究利用遗传报告基因（genetic reporter）对浆细胞进行时序标记，明确了长寿浆细胞的分布、表型、转录程序及群体结构，并计算了其更新动力学特征。研究证实，浆细胞的长寿特性是后天获得的；且在内稳态条件下，长寿浆细胞的更新不受B细胞缺失的影响，表明其更新机制不依赖于细胞竞争。本研究提出，阐明浆细胞群体动力学或可实现对其的精准调控，以达成特定研究与应用目标。