Non-antigen-specific B-cell activation following murine gammaherpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo

The murine gammaherpesvirus MHV-68 multiplies in the respiratory epithelium after intranasal inoculation, then spreads to infect B cells in lymphoid g erminal centers, Exposing B cells to MHV-68 in vitro caused an increase in cell size, up-regulation of the CD69 activation marker, and immunoglobulin M (IgM) production. The infectious process in vivo was also associated with increased CD69 expression on B cells in the draining lymph nodes and splee n, together with a rise in total serum Ig. However, whereas the in vitro ef fect on B cells was entirely T-cell independent, evidence of in vivo B-cell activation was minimal in CD4(+) T-cell-deficient (I-A(b-/-)) or CD4(+) T- cell-depleted mice. Furthermore, the Ig present at high levels in serum was predominantly of the Ige class. Surprisingly, the titer of influenza virus -specific serum IgG in previously immunized mice fell following MHV-68 infe ction, suggesting that there was relatively little activation of memory B c ells. Thus, CD4(+) T cells seemed both to amplify a direct viral activation of B cells in lymphoid tissue and to promote new Ig class switching despit e a lack of obvious cognate antigen.