Document Detail


Modulation of B-cell tolerance by murine gammaherpesvirus 68 infection: requirement for Orf73 viral gene expression and follicular helper T cells.
MedLine Citation:
PMID:  23311955     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Viruses such as Epstein-Barr virus (EBV) have been linked to mechanisms that support autoantibody production in diseases such as systemic lupus erythematosus. However, the mechanisms by which viruses contribute to autoantibody production remain poorly defined. This stems in part, from the high level of seropositivity for EBV (> 95%) and the exquisite species specificity of EBV. In this study we overcame these problems by using murine gammaherpesvirus 68 (MHV68), a virus genetically and biologically related to EBV. We first showed that MHV68 drives autoantibody production by promoting a loss of B-cell anergy. We next showed that MHV68 infection resulted in the expansion of follicular helper T (Tfh) cells in vivo, and that these Tfh cells supported autoantibody production and a loss of B-cell anergy. Finally, we showed that the expansion of Tfh cells and autoantibody production was dependent on the establishment of viral latency and expression of a functional viral gene called Orf73. Collectively, our studies highlighted an unexpected role for viral latency in the development of autoantibodies following MHV68 infection and suggest that virus-induced expansion of Tfh cells probably plays a key role in the loss of B-cell anergy.
Authors:
Stephen B Gauld; Jessica L De Santis; Joseph M Kulinski; Jennifer A McGraw; Steven M Leonardo; Elizabeth A Ruder; Weston Maier; Vera L Tarakanova
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-07-01     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  197-204     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantibodies / immunology
B-Lymphocytes / immunology*,  virology
Cell Proliferation
Cells, Cultured
Clonal Anergy / immunology
Coculture Techniques
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Host-Pathogen Interactions / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Mutation
Rhadinovirus / genetics,  immunology*,  physiology
T-Lymphocytes, Helper-Inducer / immunology*,  virology
Viral Proteins / genetics,  immunology*,  metabolism
Virus Latency / genetics,  immunology
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Orf73 protein, Murid herpesvirus 4; 0/Viral Proteins
Comments/Corrections

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