title: Concerted effect of lymphopenia, viraemia and T-cell activation on Fas expression of peripheral B cells in HIV-1-infected patients.
abstract: OBJECTIVE
  Decreased memory B-cell maintenance during HIV-1 infection has been associated with the viraemia-induced accumulation of activated memory B cells, sensitive to Fas-mediated apoptosis. We aimed at clarifying whether other B-cell subsets might also be affected by an increased Fas expression in HIV-1-infected patients, and we studied the possible contribution of viraemia, lymphopenia or T-cell activation in Fas upregulation on B cells. We analysed whether Fas upregulation might have collaborative effects with the dysregulation of other B-cell modulatory molecules, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) and programmed cell death protein 1 (PD-1), on B-cell homeostasis.
  
  
  METHODS
  Fas, LAIR1 and PD-1 were analysed on B-cell subpopulations in HIV-1-infected patients who were treatment naive, nonlymphopenic; antiretroviral therapy (ART)-treated, nonlymphopenic; or ART-treated, lymphopenic or in noninfected controls.
  
  
  METHODS
  Flow cytometry was used to study B-cell subsets and Milliplex for serum cytokines.
  
  
  RESULTS
  Fas expression increased on all B-cell subpopulations of viraemic or lymphopenic individuals. The decreased ratio of resting memory B cells and their increased Fas expression were not normalized by ART. Cytokines associated with T-cell activation might influence Fas expression on the naive and transitional B cells. LAIR1 expression decreased in all HIV-1-infected patients, but only on memory B cells, whereas PD-1 increased on resting memory B cells in viraemic patients.
  
  
  CONCLUSIONS
  Fas is regulated by the concerted action of viraemia, lymphopenia and T-cell activation during HIV-1 infection, and Fas expression is altered on all peripheral B-cell subsets. Resting memory B-cell homeostasis shows the highest sensitivity to HIV-1-induced perturbations.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Nobles väg 16, Sweden. Bence.Rethi@ki.se
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.forename: Stefano
authors.initials: S
authors.lastname: Sammicheli
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.forename: Simone
authors.initials: S
authors.lastname: Pensieroso
authors.forename: Bo
authors.initials: B
authors.lastname: Hejdeman
authors.forename: Danika
authors.initials: D
authors.lastname: Schepis
authors.forename: Pham H
authors.initials: PH
authors.lastname: Thang
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
mesh_terms: D000328:Adult; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D014766:Viremia / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D019014:fas Receptor; C108073:leukocyte-associated immunoglobulin-like receptor 1