Antibody responsiveness during immunization and challenge of genetically modified antibody responder mice with murine hepatitis virus 3

The aim of this study was to evaluate some immunological patterns involved in natural and acquired resistance against MHV3 using the original model of genetically modified lines of mice selected for high (H(III)) and low (L(III)) antibody responsiveness. As previously shown, a lower pre-existing anti-MHV antibody level was found in susceptible H(III) mice as compared to resistant L(III) mice. Mortality rates of the F(1) (H×L) hybrids and F(2) and backcross segregants reflected co-dominance of both characters and the survivors had higher pre-existing anti-MHV antibody titers. The present data show that both lines had the potential to synthesize antibodies and that the resistance acquired by the susceptible H(III) mice paralleled the antibody synthesis. Nevertheless, higher antibody titers were necessary to confer resistance in H(III) mice than in L(III) ones. When compared to uvMHV3, a single immunization with a related infectious MHV strain induced a higher antibody synthesis and led the H(III) mice to resist the MHV3 challenge. A direct correlation between the antibody level and resistance to infection was always observed in H(III) mice. Although mounting a Th2 response as indicated by IgG1 responses, they were also able to readily synthesize large amounts of IgG2a antibodies after immunization or during infection, reflecting a Th1 response. The transfer of anti-MHV antibodies to susceptible H(III) mice was capable of conferring resistance to MHV3, providing the antibodies were present before virus infection and in large amounts. The resistance and the survival time of these animals increased with the level of antibody administered. If these direct and clear data suggest that H(III) mice can acquire resistance through antibodies, the basis of the resistance of the resistant L(III) mice may rely on mechanisms less dependent on antibodies.