Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence.
Immunity
; 57(3): 600-611.e6, 2024 Mar 12.
Article
en En
| MEDLINE
| ID: mdl-38447570
ABSTRACT
Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist for decades, providing antigen-specific long-term protection. We developed a mathematical framework to explore the dynamics of plasma cell removal and its regulation by survival factors. Analyses of antibody persistence following hepatitis A and B and HPV vaccination revealed specific patterns of longevity and heterogeneity within and between responses, implying that this process is fine-tuned near a critical "flat" state between two dynamic regimes. This critical state reflects the tuning of rates of the underlying regulatory network and is highly sensitive to variation in parameters, which amplifies lifespan differences between cells. We propose that fine-tuning is the generic outcome of competition over shared survival signals, with a competition-based mechanism providing a unifying explanation for a wide range of experimental observations, including the dynamics of plasma cell accumulation and the effects of survival factor deletion. Our theory is testable, and we provide specific predictions.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Plasmáticas
/
Longevidad
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article