RESUMO
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.
Assuntos
Autoanticorpos/fisiologia , Imunoglobulina G/biossíntese , Isotipos de Imunoglobulinas/imunologia , Animais , Anticorpos Monoclonais , Isotipos de Imunoglobulinas/biossíntese , Memória Imunológica/imunologia , Vírus da Influenza A , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Recidiva , Fator Reumatoide/fisiologiaRESUMO
Repeated influenza virus infection induces the production of dominantly IgG2a-type virus-specific antibodies as well as the appearance of IgG2a-reactive autoantibodies in BALB/c mice characterized by low spontaneous rheumatoid factor-type autoantibody production. IgG2a-reactive autoantibody-producing hybridomas could be isolated from the spleen of influenza virus-infected BALB/c mice. The mAb produced by these clones represent not only IgM but also IgG and IgA isotypes and show strong isotype or isoallotype specificity. The common functional property of these autoantibodies is their preferential- and high-affinity binding to complexed, solid-phase-bound or heat-aggregated IgG2a when compared to native soluble or cell-bound IgG2a. The mechanism of induction and the possible biological function of these autoantibodies are discussed in the light of their fine specificity and functional properties.