The pathogenic human monoclonal anti-DNA that induces experimental systemic lupus erythematosus in mice is encoded by a VH4 gene segment

Ari Waisman, Yehuda Shoenfeld, Miri Blank, Pedro J. Ruiz, Edna Mozes

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human anti-DNA IgM mAb that was derived from a patient with cold agglutinln disease. The latter antl-DNA mAb expresses the common Idiotype (Id) designated 16/6 Id. The original human hybridoma 16/6 that secreted an IgM antibody that bound ssDNA and carried the 16/6 Id had switched in culture to secrete an IgG molecule. Herein we show that the IgG 16/6 antibody contains the previously reported characteristics of the original IgM 16/6 mAb: It expresses the 16/6 Id and is capable of inducing experimental SLE in susceptible mouse strains. The identity of the IgG 16/6 anti-DNA mAb to the orginal IgM mAb was shown both by serological techniques and at the T cell level. The human IgG 16/6 mAb was found to be encoded by a germline gene from the human VH4 gene family, with high similarity to the germline gene VH4.21 that was previously shown to code for anti-DNA antibodies isolated from SLE patients. The VH4.21 germline gene was found to also code for most antibodies with cold agglutinin activity that were isolated from patients with cold agglutinin disease.

Original languageEnglish
Pages (from-to)689-696
Number of pages8
JournalInternational Immunology
Volume7
Issue number4
DOIs
StatePublished - Apr 1995
Externally publishedYes

Keywords

  • Autoimmune disease
  • Pathogenic mAb
  • V gene sequence

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