Different isotype profiles of virus-specific antibodies in acute and persistent lymphocytic choriomeningitis virus infection in mice.

The humoral immune response to lymphocytic choriomeningitis virus (LCMV) was analysed by the use of a sensitive ELISA. Our results show that LCMV carriers of the C3H strain, previously believed to be completely tolerant to the virus, do in fact produce LCMV-specific antibodies and, moreover, that a significant proportion of these antibodies belong to IgG subclasses which are considered T-cell dependent. This finding, together with the fact that T-cell deficient mice made little or no LCMV-specific antibodies, makes it reasonable to infer that C3H carriers have not only virus-primed B cells, but also virus-primed T-helper cells. However, the isotype profiles of the virus-specific antibodies detected were markedly different in carriers and in immune mice. Firstly, much greater inter-individual variation was observed in the carrier population than in the immune mice. Secondly, in immune mice IgG2a antibodies dominated the humoral response, whereas in carriers the virus-specific activity in this subclass was very low. In contrast, LCMV-specific antibodies of the IgG1 subclass were present in similar titres in immune mice and in the majority of the carriers. Evaluation of the IgG2b response revealed that most carriers had little or no LCMV-specific activity in this subclass, although a few had antibody levels comparable to those in immune mice. These findings are discussed in relation to the question of the state of immunity in LCMV carriers and its consequence for immune-complex disease.