MURINE CYTOMEGALOVIRUS INFECTION-INDUCED POLYCLONAL B-CELL ACTIVATIONIS INDEPENDENT OF CD4(-CELLS AND CD40() T)

The results of this study demonstrate that murine cytomegalovirus (MCM V) induces polyclonal B cell activation in mice during the acute phase of primary infection. First, flow cytometric analysis revealed that s urface expression of CD45R, IgM, and Ig kappa by splenocytes from MCMV -infected mice was significantly reduced with a concomitant increase i n the frequency of surface IgG-expressing cells. Second, ELIspot assay s demonstrated that the changes revealed by flow cytometry were parall eled by increases in the numbers of IgG-producing cells, especially th ose secreting IgG(2a). Third, the IgG antibodies from MCMV-infected an imals reacted against a variety of self and foreign antigens. MCMV-ind uced B cell activation was independent of CD4(+) T-cell-mediated help and CD40, since activation was observed in two models of mice deficien t for this T cell subset and in mice deficient for CD40. Reverse trans cription-polymerase chain reaction analysis showed that mRNA transcrip ts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced f ollowing infection with MCMV, but only IL-6 and IFN-gamma proteins wer e detectable by ELISA. In addition, the numbers of cells producing IL- B and IFN-gamma were significantly increased in the spleen. The magnit ude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the abse nce of IFN-gamma, surface expression and serum levels of IgG(2a) were reduced while IgG(1) expression was increased. (C) 1998 Academic Press .