title: Loss of memory (CD27) B lymphocytes in HIV-1 infection.
abstract: OBJECTIVE
  The mechanisms of B-cell dysfunction during HIV-1 infection, including polyclonal B-cell activation, are poorly understood. We studied the phenotype and the functionality of peripheral memory B cells in HIV-1-infected subjects.
  
  
  METHODS
  The phenotype of B cells and the responsiveness to T-cell dependent activation in vitro were analysed in 36 HIV-1-infected and 34 healthy subjects.
  
  
  METHODS
  Phenotyping of B and T cells was performed by FACS. IgG content was measured in plasma (by nephelometry) and cultures (by enzyme-linked immunosorbent assay) of B lymphocytes activated through CD40 or CD27 ligation. Expression of Fas and Fas ligand was performed by FACS on B-cell subpopulations from five HIV-1-infected and four uninfected subjects.
  
  
  RESULTS
  The peripheral memory (CD27) B cells were significantly reduced in HIV-1-infected subjects. The amount of memory B cells was low in both drug-naive subjects and patients undergoing antiretroviral therapy. Ex vivo expression of CD70 (CD27 ligand) on T cells was significantly higher in HIV-1-infected subjects and inversely correlated with the frequency of memory B cells. In spite of the reduced number of memory B cells, in vitro spontaneous and activation-induced IgG secretion was higher in HIV-1-infected patients than in uninfected controls. The hyperactivation status of B lymphocytes in HIV-1-infected patients was further confirmed by the finding of upregulation of Fas and FasL expression on memory B cells.
  
  
  CONCLUSIONS
  Memory B lymphocytes are depleted from peripheral blood in HIV-1-infected subjects. Our ex vivo findings suggest that persistent T-cell activation may contribute to loss of memory B cells through upregulation of Fas/FasL on these cells and terminal differentiation into plasma cells.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: De Milito
authors.forename: C
authors.initials: C
authors.lastname: Mörch
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: F
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053282:CD27 Ligand; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor