title: Non-antigen-specific B-cell activation following murine gammaherpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo.
abstract: The murine gammaherpesvirus MHV-68 multiplies in the respiratory epithelium after intranasal inoculation, then spreads to infect B cells in lymphoid germinal 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 spleen, together with a rise in total serum Ig. However, whereas the in vitro effect on B cells was entirely T-cell independent, evidence of in vivo B-cell activation was minimal in CD4(+) T-cell-deficient (I-Ab-/-) or CD4(+) T-cell-depleted mice. Furthermore, the Ig present at high levels in serum was predominantly of the IgG class. Surprisingly, the titer of influenza virus-specific serum IgG in previously immunized mice fell following MHV-68 infection, suggesting that there was relatively little activation of memory B cells. 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 despite a lack of obvious cognate antigen.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Stevenson
authors.forename: P C
authors.initials: PC
authors.lastname: Doherty
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D018142:Gammaherpesvirinae / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015704:CD4 Antigens