Abstract
Our previous work has shown that young and elderly patients with Type-2 Diabetes Mellitus (T2DM) treated with Metformin have optimal B cell function and serum antibodies specific for the seasonal influenza vaccine. In this paper, we have evaluated B cell function and the metabolic requirements of B cell antibody responses in elderly T2DM patients (E
T2DM
) taking or not Metformin, and compared to those of healthy elderly (E
H
) and healthy young (Y
H
) individuals. Results show that Metformin significantly increases
in vivo
B cell function, measured by influenza vaccine-specific serum antibodies, in E
T2DM
patients to the levels observed in E
H
and more importantly in Y
H
individuals. Metformin also decreases the frequencies of pro-inflammatory B cell subsets, as well as intrinsic inflammation and metabolic requirements of peripheral B cells from E
T2DM
. This hyper-metabolic phenotype of B cells from E
T2DM
is needed to support intrinsic inflammation, measured by the expression of transcripts for markers of the senescence-associated secretory phenotype (SASP), and the secretion of autoimmune antibodies. Importantly, B cell function in E
T2DM
patients taking Metformin is not only increased as compared to that in E
T2DM
patients not taking Metformin, but is comparable to B cell function measured in Y
H
individuals. These results altogether strongly support the anti-aging effects of Metformin on humoral immunity.