Double negative (CD19(+)IgG(+)IgD(-)CD27(-)) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients.

t. Immunosenescence is characterized by the impairment of humoral immunity with changes in the mem-ory/naive B cell compartment. In particular we have previously reported the percentage increase of aMemory IgD−CD27−(Double Negative, DN) B cell population in aged people. In this study, we have fur-ther characterized DN B cells with the aim to better understand their contribution to immunosenescence.As DN B cells show a poor ability to proliferate in vitro, we have evaluated the expression of the inhibitoryreceptors CD307d and CD22 on these cells from young and old individuals. In addition we have evalu-ated the ability to activate DN B cells by the simultaneous use of innate (CpG) and adaptive ( -Ig/CD40)ligands. Our data demonstrate that the refractoriness to proliferate of DN B cells does not depend onthe expression of inhibitory receptors, but it is due to the kind of stimulation. Indeed, when DN B cellsare stimulated engaging both BCR and TLR9, they become able to proliferate and reactivate the telome-rase enzyme. In the present study, we have also compared the telomerase activity in a group of peoplegenetically advantaged for longevity as centenarian offspring (CO) and in a group of moderate–severeAlzheimer’s disease (AD) patients, who represent a model of unsuccessful aging. Our study suggests thattelomerase reactivation of DN B cells, as well as their number and ability in activating, depend essentiallyby the biological age of the subjects studied, so the evaluation of DN B cells might allow to gain insightto healthy and unsuccessful aging.