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J Immunol. 2012 Sep 15;189(6):2965-74. doi: 10.4049/jimmunol.1201407. Epub 2012 Aug 17.

Retention of anergy and inhibition of antibody responses during acute γ herpesvirus 68 infection.

Author information

1
Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA.

Abstract

The majority of the human population becomes infected early in life by the gammaherpesvirus EBV. Some findings suggest that there is an association between EBV infection and the appearance of pathogenic Abs found in lupus. Gammaherpesvirus 68 infection of adult mice (an EBV model) was shown to induce polyclonal B cell activation and hypergammaglobulinemia, as well as increased production of autoantibodies. In this study, we explored the possibility that this breach of tolerance reflects loss of B cell anergy. Our findings show that, although anergic B cells transiently acquire an activated phenotype early during infection, they do not become responsive to autoantigen, as measured by the ability to mobilize Ca2+ following AgR cross-linking or mount Ab responses following immunization. Indeed, naive B cells also acquire an activated phenotype during acute infection but are unable to mount Ab responses to either T cell-dependent or T cell-independent Ags. In acutely infected animals, Ag stimulation leads to upregulation of costimulatory molecules and relocalization of Ag-specific B cells to the B-T cell border; however, these cells do not proliferate or differentiate into Ab-secreting cells. Adoptive-transfer experiments show that the suppressed state is reversible and is dictated by the environment in the infected host. Finally, B cells in infected mice deficient of CD4+ T cells are not suppressed, suggesting a role for CD4+ T cells in enforcing unresponsiveness. Thus, rather than promoting loss of tolerance, gammaherpesvirus 68 infection induces an immunosuppressed state, reminiscent of compensatory anti-inflammatory response syndrome.

PMID:
22904300
PMCID:
PMC3436999
DOI:
10.4049/jimmunol.1201407
[Indexed for MEDLINE]
Free PMC Article

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