TY - JOUR
T1 - The role of the 16/6 idiotype network in the induction and manifestations of systemic lupus erythematosus
AU - Walsman, Ari
AU - Mendlovic, Shlomo
AU - Ruiz, Pedro J.
AU - Zinger, Heidy
AU - Meshorer, Asher
AU - Mozes, Edna
N1 - Funding Information:
This research was supported in part by the Israel Cancer Research Fund, by the Crown Endowment Fund for immunological research at the Weizmann Institute of Science, and by the Base Research Foundation administrated by the Israel Academy of Science and Humanities. The authors would like to thank Einat Zisman and Susan Kirshner for their critical evaluation of this manuscript
PY - 1993/10
Y1 - 1993/10
N2 - Experimental systemic lupus erythematosus (SLE) has been induced in mice by immunization with either a human anti-DNA mAb bearing a common idiotype (Id) designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine antl-16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1).Moreover, mAb 5G12-4 was shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells of mice immunized with the mAb 5G12-4 proliferated significantly to the human 16/6 mAb and vice versa. Following immunization of mice with the murine mAb bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to HeLa nuclear extract proteins were detected, similarly to those observed previously upon immunization with Ab1 or Ab2. Six months following the immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickening of the Bowman's capsule and glomerular necrosis. These results show the Importance of the 16/6 Id network in the induction and progression of SLE in mice.
AB - Experimental systemic lupus erythematosus (SLE) has been induced in mice by immunization with either a human anti-DNA mAb bearing a common idiotype (Id) designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine antl-16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1).Moreover, mAb 5G12-4 was shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells of mice immunized with the mAb 5G12-4 proliferated significantly to the human 16/6 mAb and vice versa. Following immunization of mice with the murine mAb bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to HeLa nuclear extract proteins were detected, similarly to those observed previously upon immunization with Ab1 or Ab2. Six months following the immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickening of the Bowman's capsule and glomerular necrosis. These results show the Importance of the 16/6 Id network in the induction and progression of SLE in mice.
KW - Anti-DNA autoantibodies
KW - Experimental autoimmune disease
KW - Idiotypic network
UR - http://www.scopus.com/inward/record.url?scp=0027484975&partnerID=8YFLogxK
U2 - 10.1093/intimm/5.10.1293
DO - 10.1093/intimm/5.10.1293
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C2 - 8268135
AN - SCOPUS:0027484975
SN - 0953-8178
VL - 5
SP - 1293
EP - 1300
JO - International Immunology
JF - International Immunology
IS - 10
ER -