In this graduate school of Tokyo Medical and Dental University, I was given a somewhat vague but farsighted theme by a professor： "protein-DNA interaction." Within these simple words, I was given a free hand. Being curious about the etiology of connective tissue diseases, I began to study the biochemistry and pathophysiology of autoimmunity, especially the nature of anti-DNA antibodies that are the principal anti-nuclear antibodies observed in patients with systemic lupus erythematosus (SLE). My thesis was on the characterization of serum anti-DNA antibodies purified by a novel method of affinity column chromatography.¹ Thereafter, I remained involved in this fascinating field. In spite of the rapid progress in molecular immunology, the etiology of any particular systemic autoimmune disorder remains elusive at this point. Here, works on a monoclonal anti-DNA antibody performed in the laboratories of Dr. B. D. Stollar (Tufts University, Boston), Dr. Y. Kanai (University of Tokyo), and in our laboratory will be reviewed along with related articles.

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To determine the significance of Epstein-Barr virus (EBV) in the tumorigenesis of Warthin tumor, formaldehyde-fixed and paraffin-embedded specimens of 21 tumors from 18 patients were examined by polymerase chain reaction (PCR)-Southern hybridization, in situ hybridization (ISH), and immunohistochemistry. PCR-Southern hybridization revealed the presence of EBV DNA in 13 of the 21 tumors (61.9%). However, ISH for EBV RNA showed that nuclei of the neoplastic epithelial cells of all tumors were negative. Although ISH for EBV DNA revealed that the nuclei of the neoplastic epithelial cells were positive in 4 of the 21 tumors (19.0%), the positive cells were sparsely distributed and there was no evidence of monoclonal proliferation of EBV positive neoplastic epithelial cells. Moreover, immunohistochemical reactions with antibodies against latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2), were negative in all cases. Judging from these findings, we conclude that EBV does not play a major role in the tumorigenesis of Warthin tumor.

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