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Modulation of B ‐cell tolerance by Murine Gammaherpesvirus 68 infection: requirement for O rf73 viral gene expression and follicular helper T cells
Author(s) -
Gauld Stephen B.,
Santis Jessica L.,
Kulinski Joseph M.,
McGraw Jennifer A.,
Leonardo Steven M.,
Ruder Elizabeth A.,
Maier Weston,
Tarakanova Vera L.
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12069
Subject(s) - autoantibody , biology , virus , immunology , epstein–barr virus , b cell , gene , virology , autoimmunity , antibody , genetics
Summary Viruses such as E pstein– B arr 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 ( MHV 68), a virus genetically and biologically related to EBV . We first showed that MHV 68 drives autoantibody production by promoting a loss of B ‐cell anergy. We next showed that MHV 68 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 O rf73. Collectively, our studies highlighted an unexpected role for viral latency in the development of autoantibodies following MHV 68 infection and suggest that virus‐induced expansion of T fh cells probably plays a key role in the loss of B ‐cell anergy.