Dietary restriction mitigates the age-associated decline in mouse B cell receptor repertoire diversity
Carolina Monzó,
Lisonia Gkioni,
Andreas Beyer,
Dario Riccardo Valenzano,
Sebastian Grönke,
Linda Partridge
Affiliations
Carolina Monzó
Department Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, 50931 Cologne, North Rhine Westphalia, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Age-Associated Diseases (CECAD), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne, 50931 Cologne, Germany
Lisonia Gkioni
Department Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, 50931 Cologne, North Rhine Westphalia, Germany
Andreas Beyer
Cologne Excellence Cluster on Cellular Stress Responses in Age-Associated Diseases (CECAD), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne, 50931 Cologne, Germany
Dario Riccardo Valenzano
Microbiome-Host Interactions in Ageing Group, Max Planck Institute for Biology of Ageing, 50931 Cologne, North Rhine Westphalia, Germany; Evolutionary Biology/Microbiome-Host Interactions in Aging Group: Fritz Lipmann Institute - Leibniz Institute on Aging, 07745 Jena, Thuringia, Germany; Corresponding author
Sebastian Grönke
Department Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, 50931 Cologne, North Rhine Westphalia, Germany; Corresponding author
Linda Partridge
Department Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, 50931 Cologne, North Rhine Westphalia, Germany; Genetics, Evolution & Environment Group, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK; Corresponding author
Summary: Aging impairs the capacity to respond to novel antigens, reducing immune protection against pathogens and vaccine efficacy. Dietary restriction (DR) extends life- and health span in diverse animals. However, little is known about the capacity of DR to combat the decline in immune function. Here, we study the changes in B cell receptor (BCR) repertoire during aging in DR and control mice. By sequencing the variable region of the BCR heavy chain in the spleen, we show that DR preserves diversity and attenuates the increase in clonal expansions throughout aging. Remarkably, mice starting DR in mid-life have repertoire diversity and clonal expansion rates indistinguishable from chronic DR mice. In contrast, in the intestine, these traits are unaffected by either age or DR. Reduced within-individual B cell repertoire diversity and increased clonal expansions are correlated with higher morbidity, suggesting a potential contribution of B cell repertoire dynamics to health during aging.
