Chronic and later onset dietary restriction mitigate the age-associated decline in the mouse B cell receptor repertoire diversity

Ageing impairs the capacity of the organism to respond to novel antigens. Ageing individuals experience a decline in adaptive immune function, which translates into decreased protection against pathogens and decreased efficacy of vaccines. Dietary restriction (DR) is the most robust experimental regimen to extend life- and health span in various animal models and initiation of DR at older ages can recapture some of the health benefits of chronic DR. However, little is known about the effect of chronic or later onset DR on the ageing immune repertoire. Here, we report results of the first study of B cell receptor repertoire ageing of DR mice, and mice where DR was applied at the age of 16 months. DR delays both the age-associated decline of within-individual spleen repertoire diversity, as well as the increase of clonal expansions. Further, mice starting DR at 16 months have spleen repertoire diversity and clonal expansion rates indistinguishable from mice under chronic DR. Thus, DR-mediated B cell receptor repertoire responsiveness is predominantly characterised by the preservation of a more diverse spleen repertoire, which is less prone to clonal expansions. The association of reduced within-individual diversity and increased clonal expansions with a higher morbidity index provides the first direct evidence for a functional implication of B cell repertoire dynamics in the health benefits of chronic DR treatment, as well as 16 months later-onset DR.