biostudies-literaturevan Grevenynghe JNIDA NIH HHSNIAID NIH HHSCIHR3877-88https://www.ebi.ac.uk/biostudies/studies/S-EPMC3195482biostudies-literatureUnknown121(10)Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cThe Journal of clinical investigationLoss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis.PMC3195482DP1 DA028871P01 AI076174Cubas RABoulassel MRHaddad EKPeretz YProcopio FAChomont Nvan Grevenynghe JBalderas RSNoto ASaid EAHe ZDupuy FPSekaly RPTremblay CLRouty JPFilali-Mouhim ADaFonseca SfalseLoss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis.Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B c2011-01-01T00:00:00Z2011 Oct2025-04-26T22:53:53.897Z2019-03-27T00:45:04ZS-EPMC31954822192646310.1172/jci5921110.1172/JCI59211