title: Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection.
abstract: OBJECTIVE
  To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection.
  
  
  METHODS
  Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction.
  
  
  METHODS
  Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication.
  
  
  RESULTS
  : Although the emergence of exhausted, CD21 tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21 activated memory B cells was lower in spontaneous controllers.
  
  
  CONCLUSIONS
  Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA.
authors.forename: Gaia
authors.initials: G
authors.lastname: Sciaranghella
authors.forename: Neath
authors.initials: N
authors.lastname: Tong
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mahan
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D000328:Adult; D053264:B-Cell Activating Factor / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017464:Receptors, Complement 3d / Q000276:immunology*; D014766:Viremia / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D017464:Receptors, Complement 3d; D019014:fas Receptor