The pathogenic human monoclonal anti-DNA that induces experimental systemic lupus erythematosus in mice is encoded by a V_H4 gene segment

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 V_H4 gene family, with high similarity to the germline gene V_H4.21 that was previously shown to code for anti-DNA antibodies isolated from SLE patients. The V_H4.21 germline gene was found to also code for most antibodies with cold agglutinin activity that were isolated from patients with cold agglutinin disease.