Document Detail


Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection.
MedLine Citation:
PMID:  23135171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection.
DESIGN: 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.
CONCLUSION: 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:
Gaia Sciaranghella; Neath Tong; Alison E Mahan; Todd J Suscovich; Galit Alter
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-06-13     Revised Date:  2013-08-12    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-80     Citation Subset:  IM; X    
Affiliation:
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02129, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD95 / immunology*
B-Cell Activating Factor / immunology
B-Lymphocytes / immunology*
Female
Flow Cytometry
HIV Infections / immunology*
HIV-1 / physiology*
Humans
Immunophenotyping
Lymphocyte Activation / immunology
Male
Middle Aged
Receptors, Complement 3d / immunology*
Viremia / immunology*
Virus Replication / immunology*
Grant Support
ID/Acronym/Agency:
5P30AI060354/AI/NIAID NIH HHS; R01 AI080289/AI/NIAID NIH HHS; R01AI080289/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/B-Cell Activating Factor; 0/Receptors, Complement 3d
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