Residual LCMV antigen in transiently CD4+ Tcell-depleted mice induces high levels of virus-specific antibodies but only limited B-cell memory.

Abstract

Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (Arm) induces an acute infection with rapid virus clearance by CD8+ Tcells independently of CD4+ Tcell help. Residual viral antigen may, however, persist for a prolonged time. Here, we demonstrate that mice that had been transiently depleted of CD4+ Tcells during acute LCMV Arm infection generated high levels of virus-specific IgG antibodies (Ab) after viral clearance. Robust induction of LCMV-specific IgG after transient CD4+ Tcell depletion was dependent on Fcγ receptors but not on the complement receptors CD21/CD35. In contrast to the potent production of LCMV-specific IgG, the generation of LCMV-specific isotype-switched memory Bcells after transient CD4+ Tcell depletion was considerably reduced. Moreover, mice depleted of CD4+ Tcells during acute infection were strongly impaired in generating a secondary LCMV-specific Bcell response upon LCMV rechallenge. In conclusion, our data indicate that LCMV antigen depots after viral clearance were capable of inducing high levels of virus-specific IgG. They failed, however, to induce robust virus-specific Bcell memory revealing a previously unappreciated dichotomy of specific Ab production and memory cell formation after priming with residual antigen.