title: Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.
abstract: OBJECTIVE
  Microbial translocation and chronic immune activation were previously shown to be associated with impairment of T cell functions and disease progression during infection with human immunodeficiency virus type-1 (HIV-1); however, their impact on B cell function and number remains unknown. By measuring markers of immune activation and molecules involved in apoptosis regulation, we have evaluated the association between microbial translocation and loss of memory B cells in HIV-1-infected patients.
  
  
  METHODS
  Markers of activation [the interleukin-21 receptor (IL-21R) and CD38] and apoptosis (Bim, Bcl-2 and annexin V) were measured in B cell subpopulations by multicolour flow cytometry. Levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS), measures of microbial translocation, were determined in plasma. Purified B cells were also exposed in vitro to Toll-like receptor (TLR) ligands.
  
  
  RESULTS
  IL-21R expression was higher in cells from HIV-1-infected patients, compared with control subjects, with the highest levels in nontreated patients. An inverse correlation was observed between IL-21R expression and percentages of circulating resting memory (RM) B cells. IL-21R-positive memory B cells were also more susceptible to spontaneous apoptosis and displayed lower levels of Bcl-2. It is interesting that the levels of sCD14, which are increased during HIV-1 infection, were correlated with decreased percentages of RM B cells and high IL-21R expression. In the plasma of HIV-1-infected individuals, a correlation was found between sCD14 and LPS levels. TLR activation of B cells in vitro resulted in IL-21R up-regulation.
  
  
  CONCLUSIONS
  Microbial translocation and the associated immune activation during HIV-1 infection may lead to high expression levels of the IL-21R activation marker in RM B cells, a feature associated with increased apoptosis and a reduced number of these cells in the circulation.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Venhälsan, South Hospital, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Ruffin
authors.forename: R
authors.initials: R
authors.lastname: Lantto
authors.forename: S
authors.initials: S
authors.lastname: Pensieroso
authors.forename: S
authors.initials: S
authors.lastname: Sammicheli
authors.forename: B
authors.initials: B
authors.lastname: Hejdeman
authors.forename: B
authors.initials: B
authors.lastname: Rethi
authors.forename: F
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D000367:Age Factors; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D018988:Bacterial Translocation / Q000502:physiology; D015415:Biomarkers; D016022:Case-Control Studies; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D053655:Receptors, Interleukin-21 / Q000378:metabolism*; D013548:Sweden
chemical_list: D015415:Biomarkers; D053655:Receptors, Interleukin-21