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

Background: We have previously reported the increase of IgD-CD27- (Double Negative, DN) B cell population in the aged. These memory B cells have short telomeres and poor abilities to proliferate in vitro. Here, we investigated whether the low ability of DN B cells to proliferate depends on the expression levels of the CD307d and CD22 inhibitory receptors or whether DN B cells can proliferate and reactivate telomerase by 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 TRAP and 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 not related with the different ability of DN to be activated in the young and elderly. Moreover, CpG/α-IgG/α-CD40 (and not CpG or α-IgG/α-CD40) stimulation induces DN B cell proliferation in both young and elderly subjects. Furthermore, DN B cell telomerase activity in young, elderly, CO and AD patients, mirrors the age and health status of the subjects studied. Indeed, young donors show the highest levels of RTA, whereas AD patients 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 of DN B cells during aging. We demonstrate that the low ability of DN cells to proliferate depends on RTA and not on the expression of inhibitory receptors.