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Modulation of B cell tolerance by MHV68 infection: Requirement for Orf73 viral gene expression and follicular helper T cells.
MedLine Citation:
PMID:  23311955     Owner:  NLM     Status:  Publisher    
Viruses such as Epstein-Barr Virus (EBV) have been linked to mechanisms that support autoantibody production in diseases such as lupus. 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 MHV68 infection resulted in the expansion of follicular helper T (T(FH) ) cells in vivo, and that these T(FH) cells supported autoantibody production and a loss of B cell anergy. Finally, we showed that the expansion of T(FH) 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 viral-induced expansion of T(FH) cells likely plays a key role in the loss of B cell anergy. © 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
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     Date:  2013-1-12
Journal Detail:
Title:  Immunology     Volume:  -     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Division of Allergy/Immunology, Department of Pediatrics, Medical College of Wisconsin, The Children's Research Institute, Milwaukee, WI, 53226.
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