VESICULAR STOMATITIS-VIRUS INDIANA GLYCOPROTEIN AS A T-CELL-DEPENDENTAND T-CELL-INDEPENDENT ANTIGEN

The neutralizing immunoglobulin M (IgM) response to vesicular stomatit is virus (VSV) has been shown to be largely T-cell independent in seve ral T-cell-deficient models of mice. By using different antigen forms of VSV, VSV antigen doses could be graded in vivo (infectious much gre ater than UV inactivated > formalin inactivated). The present study re veals a T-cell-dependent component of the neutralizing IgM response in nude mice given intravenous injections of low doses of noninfectious UV-inactivated VSV serotype Indiana (VSV-IND) only if the mice are tra nsfused with VSV-IND-specific helper T cells. Instead, nude mice immun ized with infectious VSV, which leads to greater antigen doses in vivo , were able to mount an IgM response in the absence of T cells. These results indicate that the IgM response to low doses of VSV-IND glycopr otein (G) is T-cell dependent. Nude mice immunized with infectious VSV also made a variable but low VSV-IND-neutralizing IgG response. A VSV -IND matrix (M)-specific helper T-cell line rendered this response mor e consistent, much higher, and longer lasting. Thus (i) VSV-G induces a mostly T-cell-independent but partially T-cell-dependent IgM (the la tter can be visualized best at low doses of antigen) and (ii) the anti body response to VSV in nude mice proceeds through steps, i.e., IgM an d IgG, that are dose dependent. The results suggest that the predomina nt role of helper T cells may be to expand and maintain the individual steps of differentiating B cells.