Double Negative (CD19+IgG+IgD-CD27-) B Lymphocytes:A New Insight from Telomerase in Healthy Elderly, in CentenarianOffspring, and in Alzheimer’s Disease Patients

Background: We have previously reported the increase of IgD-CD27-(Double Negative, DN) B cell population in the aged. These memory Bcells have short telomeres and poor abilities to proliferate in vitro. Here,we investigated whether the low ability of DN B cells to proliferatedepends on the expression levels of the CD307d and CD22 inhibitoryreceptors or whether DN B cells can proliferate and reactivate telomeraseby the engagement of both innate and adaptive immune receptors.Methods: Phenotypic analyses were made by using flow cytometry.Quantitative analysis of telomerase activity was made by using a TRAPand a photometric enzyme immunoassay in young, healthy elderly,centenarian offspring (CO), and Alzheimer’s disease patients (AD).Results: We show that CD307d and CD22 expression levels are notrelated with the different ability of DN to be activated in the young andelderly. Moreover, CpG/α-IgG/α-CD40 (and not CpG or α-IgG/α-CD40)stimulation induces DN B cell proliferation in both young and elderlysubjects. Furthermore, DN B cell telomerase activity in young, elderly, COand AD patients, mirrors the age and health status of the subjects studied.Indeed, young donors show the highest levels of RTA, whereas ADpatients the lowest. Healthy elderly and CO show lower levels than young,with a slight increase of activity in CO vs. elderly.Conclusions: Our present data add new information to our knowledge ofDN B cells during aging. We demonstrate that the low ability of DN cells toproliferate depends on RTA and not on the expression of inhibitoryreceptors.