Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Marcus James Robinson; Zhoujie Ding; Mark R Dowling; Danika L Hill; Rosela H Webster; Craig McKenzie; Catherine Pitt; Kristy O'Donnell; Jesse Mulder; Erica Brodie; Philip D Hodgkin; Nick C Wong; Isaak Quast; David M Tarlinton

doi:10.1016/j.immuni.2023.04.015

Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Immunity. 2023 Jul 11;56(7):1596-1612.e4. doi: 10.1016/j.immuni.2023.04.015. Epub 2023 May 9.

Affiliations

¹ Department of Immunology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia. Electronic address: marcus.robinson@monash.edu.
² Department of Immunology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia.
³ Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, VIC 3000, Australia; Immunology Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3050, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
⁴ Department of Immunology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia; Monash Bioinformatics Platform, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia.
⁵ Immunology Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3050, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
⁶ Monash Bioinformatics Platform, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia.
⁷ Department of Immunology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC 3004, Australia. Electronic address: david.tarlinton@monash.edu.

PMID: 37164016
DOI: 10.1016/j.immuni.2023.04.015

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.

Keywords: MCL1; antibody; antibody-producing cell; competition; niche; plasma cell; plasmablast; rituximab; survival; turnover.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibody-Producing Cells
Longevity*
Plasma Cells*