T-Independent Activation of B Cells by Vesicular Stomatitis Virus: No Evidence for the Need of a Second Signal

Vesicular stomatitis virus (VSV) induces a T helper cell-independent IgM antibody response, whereas the IgG response is strictly T helper cell dependent. Since VSV induces B cells in complete absence of T helper cells, the question arises as to whether this induction occurs in the absence of a second signal or whether it depends upon an alternative or replacing signal 2. We therefore asked whether VSV has polyclonal B cell stimulator activity and/or whether B cell induction by VSV needs costimulation via complement or tumor necrosis factor (TNF) receptor or by natural killer (NK) cell activity.In vitroB cell proliferation assays and analysis of thein vivoantibody response in CD40-deficient mice excluded that VSV has properties of a polyclonal B cell stimulator. C3 depletion by cobra venom factor and application of anti-complement receptor antibodies showed that the T-independent IgM response was largely C3-independent except under very limiting antigen doses. Immunization of TNF receptor-deficient mice showed a normal anti-VSV IgM response, and in a cytotoxicity assay on YAC target cells there was no evidence for NK cell activation by VSV. Thus, VSV seems to induce B cells without polyclonal activation and/or C3, TNF, or NK cells functioning as a replacing second signal.