Murine cytomegalovirus infection-induced polyclonal B cell activation is independent of CD4+ T cells and CD40

Abstract

The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First, flow cytometric analysis revealed that surface expression of CD45R, IgM, and Igκ by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG(2a). Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4+ T- cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-γ were rapidly induced following infection with MCMV, but only IL-6 and IFN-γ proteins were detectable by ELISA. In addition, the numbers of cells producing IL-6 and IFN-γ were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-γ. In the absence of IFN-γ, surface expression and serum levels of IgG(2a) were reduced while IgG1 expression was increased.