Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus

Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology, vaccine development as well as health policy. Long-lived plasma cells, which have recently been shown to reside in...

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Main Authors:	Andraud, Mathieu, Lejeune, Olivier, Musoro, Jammbe Z., Ogunjimi, Benson, Beutels, Philippe, Hens, Niel
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291529/

id	pubmed-3291529
recordtype	oai_dc
spelling	pubmed-32915292012-03-06 Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus Andraud, Mathieu Lejeune, Olivier Musoro, Jammbe Z. Ogunjimi, Benson Beutels, Philippe Hens, Niel Research Article Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology, vaccine development as well as health policy. Long-lived plasma cells, which have recently been shown to reside in survival niches in the bone marrow, are instrumental in the process of immunity induction and persistence. We developed a mathematical model, assuming two antibody-secreting cell subpopulations (short- and long-lived plasma cells), to analyze the antibody kinetics after HAV-vaccination using data from two long-term follow-up studies. Model parameters were estimated through a hierarchical nonlinear mixed-effects model analysis. Long-term individual predictions were derived from the individual empirical parameters and were used to estimate the mean time to immunity waning. We show that three life spans are essential to explain the observed antibody kinetics: that of the antibodies (around one month), the short-lived plasma cells (several months) and the long-lived plasma cells (decades). Although our model is a simplified representation of the actual mechanisms that govern individual immune responses, the level of agreement between long-term individual predictions and observed kinetics is reassuringly close. The quantitative assessment of the time scales over which plasma cells and antibodies live and interact provides a basis for further quantitative research on immunology, with direct consequences for understanding the epidemiology of infectious diseases, and for timing serum sampling in clinical trials of vaccines. Public Library of Science 2012-03-01 /pmc/articles/PMC3291529/ /pubmed/22396639 http://dx.doi.org/10.1371/journal.pcbi.1002418 Text en Andraud et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Andraud, Mathieu Lejeune, Olivier Musoro, Jammbe Z. Ogunjimi, Benson Beutels, Philippe Hens, Niel
spellingShingle	Andraud, Mathieu Lejeune, Olivier Musoro, Jammbe Z. Ogunjimi, Benson Beutels, Philippe Hens, Niel Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
author_facet	Andraud, Mathieu Lejeune, Olivier Musoro, Jammbe Z. Ogunjimi, Benson Beutels, Philippe Hens, Niel
author_sort	Andraud, Mathieu
title	Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
title_short	Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
title_full	Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
title_fullStr	Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
title_full_unstemmed	Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
title_sort	living on three time scales: the dynamics of plasma cell and antibody populations illustrated for hepatitis a virus
description	Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology, vaccine development as well as health policy. Long-lived plasma cells, which have recently been shown to reside in survival niches in the bone marrow, are instrumental in the process of immunity induction and persistence. We developed a mathematical model, assuming two antibody-secreting cell subpopulations (short- and long-lived plasma cells), to analyze the antibody kinetics after HAV-vaccination using data from two long-term follow-up studies. Model parameters were estimated through a hierarchical nonlinear mixed-effects model analysis. Long-term individual predictions were derived from the individual empirical parameters and were used to estimate the mean time to immunity waning. We show that three life spans are essential to explain the observed antibody kinetics: that of the antibodies (around one month), the short-lived plasma cells (several months) and the long-lived plasma cells (decades). Although our model is a simplified representation of the actual mechanisms that govern individual immune responses, the level of agreement between long-term individual predictions and observed kinetics is reassuringly close. The quantitative assessment of the time scales over which plasma cells and antibodies live and interact provides a basis for further quantitative research on immunology, with direct consequences for understanding the epidemiology of infectious diseases, and for timing serum sampling in clinical trials of vaccines.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291529/
_version_	1611509752297160704

Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus

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