Virus or a hapten-carrier complex can activate autoreactive B cells by providing linked T help.

We 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 either by a classical carrier determinant or a virus.