In vivo manipulation of IgG2a production by isotype-specific autoantibodies.

Repeated intranasal infection of Balb/c mice with A/PR/8 influenza virus induced an intense antiviral IgG response dominated by the IgG2a subclass, and accompanied by the appearance of IgG2a reactive autoantibodies. Cells producing IgG2a reactive autoantibodies could then be cloned as hybridomas from the virus infected animals. Monoclonal antibodies produced by selected hybridomas U28, Z26 and Z41 produced IgM-type antibodies with strong specificity for the IgG2a isotype bearing "a" allotypic determinants on the Fc region. These IgG2a specific autoantibodies showed highly preferred binding to solid phase bound or aggregated IgG2a, compared to soluble native IgG2a. Based on these characteristics they were classified as mono-reactive rheumatoid factor (RF)-like autoantibodies. Passive administration of IgM type IgG2a-specific autoantibodies to influenza virus infected animals resulted in a long-term reduction in the secondary antiviral response. This could be demonstrated by decreased virus neutralizing activity of the serum and diminished level of IgG2a-type anti-viral antibodies. A similar effect was observed in Balb/c mice contact sensitized with oxazolone: passive administration of RF-like antibodies resulted in reduced IgG2a response to oxazolone while the level of antibodies belonging to other isotypes was not influenced. These results suggest an isotype-specific regulatory function of these RF-like autoantibodies presumably acting via antigen-antibody complexes.