A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes.
Antibodies directed against self-Ags are frequently considered detrimental, and have been shown to play a pathogenic role in certain autoimmune diseases. However, the presence of autoreactive Abs in normal individuals suggests that some autoantibodies could participate in normal physiology. Our previous studies demonstrated that monoclonal autoantibodies SCH94.03 and SCH94.32, generated from the splenocytes of uninfected SJL/J mice injected with normal homogenized spinal cord, promote central nervous system remyelination when passively transferred into syngeneic mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we show that these two monoclonal autoantibodies are identical, and have phenotypic characteristics of natural autoantibodies. By using a solid phase assay system, SCH94.03 and SCH94.32 showed reactivity toward several protein Ags and chemical haptens, with prominent reactivity toward spectrin, (4-hydroxy-3-nitrophenyl)acetyl, and fluorescein. Sequence analysis showed that both SCH94.03 and SCH94.32 were encoded by identical germline Ig light chain V kappa 10/J kappa 1 and heavy chain V23/DFL16.1/JH2 genes, with no definitive somatic mutations. These results indicate that a natural autoantibody participates in a beneficial physiologic response to central nervous system injury.
Miller
D J
DJ
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905.
Rodriguez
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000916:Antibody Diversity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002490:Central Nervous System / Q000276:immunology / Q000502:physiology; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005803:Genes, Immunoglobulin; D007113:Immunity, Innate; D051379:Mice; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C101676:SCH94.03 monoclonal antibody; D004247:DNA