THE ROLE OF THE 16 6 IDIOTYPE NETWORK IN THE INDUCTION AND MANIFESTATIONS OF SYSTEMIC LUPUS-ERYTHEMATOSUS/

Experimental systemic lupus erythematosus (SLE) has been induced in mi ce by immunization with either a human anti-DNA mAb bearing a common i diotype (ld) designated 16/6 ld (antibody 1, Abl) or with a murine ant i-16/6 ld mAb (Ab2). In the present study a murine mAb (5Gl2-4, Ab3) t hat bears the 16/6 ld and binds to DNA was produced and was found to b ind rabbit anti-16/6 ld sera and murine anti-16/6 ld mAb similarly to the human mAb 16/6 ld (Abl). Moreover, mAb 5Gl2-4 was shown to share T cell epitopes with the human 16/6 ld mAb, since lymph node cells of m ice immunized with the mAb 5Gl2-4 proliferated significantly to the hu man 16/6 mAb and vice versa. Following immunization of mice with the m urine mAb bearing the 16/6 ld, antibodies to dsDNA, ssDNA, 16/6 ld, an ti-16/6 ld, and to HeLa nuclear extract proteins were detected, simila rly to those observed previously upon immunization with Ab1 or Ab2. Si x months following the immunization, the mice exhibited leukopenia, in creased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickeni ng of the Bowman's capsule and glomerular necrosis. These results show the importance of the 16/6 ld network in the induction and progressio n of SLE in mice.