Chronic and later onset dietary restriction mitigate the age-associated decline in the mouse B cell receptor repertoire diversity: effects on the microbiome
Ageing impairs the capacity of mammals to respond to novel antigens. Ageing individuals experience a decline in adaptive immune function, resulting in decreased protection against pathogens and decreased efficacy of vaccines. Dietary restriction (DR) extends life- and health span in diverse animals, and initiation of DR even at older ages can recapture some of its health benefits. However, little is known about the capacity of DR to combat the decline in immune function. Here, we measured changes in the B cell receptor (BCR) repertoire of DR (from 3 months) and control mice during ageing, by sequencing the variable region of the BCR heavy chain. We also analysed the BCR repertoire in mice where DR was applied only from mid-life (16 months), to determine if DR can have acute beneficial effects later in life. DR maintained within-individual spleen BCR repertoire diversity and attenuated the increase in clonal expansions during ageing. Furthermore, mice starting DR at 16 months had spleen repertoire diversity and clonal expansion rates indistinguishable from mice under DR started at 3 months. In contrast, in the ileum of the intestine, these traits were unaffected by either age or DR. There was an association of reduced within-individual B cell repertoire diversity and increased clonal expansions with higher morbidity in individual mice, suggesting a potential contribution of B cell repertoire dynamics to health during ageing. Finally, the 16S region of the microbiome of these mice was evaluated and compared to their B cell receptor repertoires