Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan
- Author(s)
- Robinson, MJ; Ding, Z; Dowling, MR; Hill, DL; Webster, RH; McKenzie, C; Pitt, C; O'Donnell, K; Mulder, J; Brodie, E; Hodgkin, PD; Wong, NC; Quast, I; Tarlinton, DM;
- Details
- Publication Year 2023-05-04,Volume 56,Issue #7,Page 1596-1612 e4
- Journal Title
- Immunity
- Abstract
- Antibodies produced by antibody-secreting plasma cells (ASCs) underlie multiple forms of long-lasting immunity. 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.
- Publisher
- Cell Press
- Keywords
- Mcl1; antibody; antibody-producing cell; competition; niche; plasma cell; plasmablast; rituximab; survival; turnover
- Research Division(s)
- Immunology
- PubMed ID
- 37164016
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2023.04.015
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-07-21 09:50:17
Last Modified: 2023-07-21 09:52:18