Synergistic activation of cells by Epstein-Barr virus and B-cell growth factor.
Infection with Epstein-Barr virus (EBV) is initiated by virus binding to the C3dg-C3d receptor CR2. Several workers have implicated this receptor in the control of B-cell activation by examining the effects of antibodies to CR2 and isolated C3d on B-cell proliferation and differentiation. We report here on the activating effects of irradiated EBV, which retains its capacity to bind to CR2 but loses its ability to function as a T-independent B-cell activator. EBV synergized with B-cell growth factor in the induction of uptake of tritiated thymidine by T cell-depleted leukocytes from seronegative donors but did not induce secretion of immunoglobulin. Synergism could be inhibited with an anti-viral antibody that inhibited binding of EBV to CR2. No similar synergism was found between EBV and recombinant interleukin 2, interleukin 1 alpha, or gamma interferon or with the lipid A fraction of bacterial lipopolysaccharide. EBV may thus initiate B-cell activation as it binds to CR2. Infectious virus may, under normal circumstances, induce the cell to make those growth factors necessary to support B-cell proliferation; the difficulty of transforming cells with transfected EBV DNA may in part reflect the absence of an activation event provided by intact virus as it attaches to CR2. The synergism of EBV and B-cell growth factor more clearly distinguishes the effects of B-cell growth factor from those of interleukin 1 and interleukin 2 in other models of B-cell activation. Thus, this may be a useful model for further delineation of unique effects of B-cell growth factor on B-cell function.
D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology* / Q000382:microbiology; D001688:Biological Products / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines; D006133:Growth Substances / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000528:radiation effects; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D015847:Interleukin-4; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*; D011991:Receptors, Virus / Q000502:physiology
D001688:Biological Products; D016207:Cytokines; D006133:Growth Substances; D007136:Immunoglobulins; D008222:Lymphokines; D011991:Receptors, Virus; D015847:Interleukin-4