International Immunology, Vol. 12, No. 11, 1569-1578,
November 2000
© 2000 Japanese Society for Immunology
Induction of anti-DNA antibody with DNA–peptide complexes
Department of Microbiology and Immunology, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA
1 Present address: Department of Medicine, Division of Rheumatology, Columbia University, New York, NY 10032-3702, USA
Correspondence to: T. N. Marion
Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibodies produced by antigen-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody variable region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA–protein complexes may provide the antigenic stimulus for autoimmune anti-DNA antibody. Previously we have demonstrated that native mammalian DNA in complexes with an immunogenic DNA-binding peptide Fus1 from Trypanosoma cruzi can induce anti-DNA antibody in mice not genetically prone to autoimmune disease. The induced anti-DNA has similar specificity, structure and immunopathological function as autoimmune anti-DNA. The present experiments were designed to further characterize the immune response to DNA–peptide complexes. There was considerable variation in the antibody responses of mice from different strains to DNA–Fus1 immunizations. The range was from virtually no response in C57BL/6 mice to most robust responses in NZW mice. The full-length 52 amino acid carboxy-extension protein of ubiquitin (CEP) in T. cruzi (TCEP) protein from which Fus1 was derived functions equally well as an immunogenic carrier for DNA. Anti-DNA responses were generally weak even though anti-Fus1 and anti-TCEP responses were very strong. The results are discussed with respect to the contrasting roles of T cell help and peripheral B cell tolerance in controlling immune and autoimmune antibody responses to DNA.
Keywords: anti-DNA antibodies, autoimmunity, immunization, mice, tolerance
Transmitting editor: J. F. Kearney
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