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.

Abstract

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.