AbstractWe investigated the mechanism leading to an IgG autoantibody response in two transgenic mouse lines expressing the glycoprotein of vesicular stomatitis virus (VSV‐G). Previous experiments have shown that these animals do not mount a transgene‐specific IgG response upon stimulation with purified VSV‐G or infection with recombinant vaccinia virus expressing VSV‐G. However, infection of VSV‐G transgenic animals with wild‐type vesicular stomatitis virus, serotype Indiana, readily induced VSV‐G‐specific, neutralizing IgG autoantibodies. We have tested whether this labile state of tolerance reflected differential availability of VSV‐G‐specific T help. For this, we immunized transgenic mice with the self‐antigen VSV‐G covalently coupled to sperm‐whale myoglobulin (VSV‐G‐SWM), to provide new T helper epitopes that are linked to the B cell epitope; co‐injected uncoupled VSV‐G and SWM served as control. High titers of VSV‐G specific IgG autoantibodies were detected in serum of mice immunized with VSV‐G‐SWM but not after co‐injection of uncoupled VSV‐G and SWM. Transgenic animals depleted of CD4+T cells prior to injection of VSV‐G‐SWM failed to mount an IgG response. Priming of transgenic mice with the foreign carrier did not accelerate the IgG autoantibody response to VSV‐G‐SWM, suggesting that B cells were limiting the rate of the response. Thus, self‐reactive B cells could be triggered to produce IgG, if they received linked T help specific for a foreign carrier determinant provided
展开▼
