In vitro manipulation of human anti-DNA antibody production by anti-idiotypic antibodies conjugated with neocarzinostatin.
Anti-DNA Id, 0-81, consist of 5 to 51% of Id in human anti-ssDNA antibodies; NE-1-Id shares 2 to 20% of those in anti-dsDNA antibodies. Thus, both 0-81-Id and NE-1-Id are of the cross-reactive Id that are commonly present among anti-DNA antibodies. In order to manipulate the production of anti-DNA antibodies by human PBL, we used mouse antiidiotypic mAb or those conjugated with a cytotoxic agent, neocarzinostatin. Treatment with the conjugates caused profound suppression of anti-ssDNA and anti-dsDNA antibody synthesis related to 0-81- and NE-1-Id. This was attributed to the specific killing of the clones bearing anti-DNA Id among the lymphocytes, evidenced by the indirect rosette formation tests. The Id-mediated suppression was not solely due to selective elimination of Id-positive B cells, because 50 to 92% of anti-DNA antibodies were suppressed by treatment with the conjugates. This was supported by flow cytometry analysis that showed a decrease of anti-Id-reactive cells when T cells were treated with the conjugates. This method, then, will permit an analysis of the question as to whether T cells reactive to anti-idiotypic antibodies might participate in the regulatory mechanism for anti-DNA production and, in addition, may lead to a new therapy for SLE.
Sasaki
T
T
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Tamate
E
E
Muryoi
T
T
Takai
O
O
Yoshinaga
K
K
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000502:physiology; D000922:Immunotoxins / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D007130:Immunoglobulin Idiotypes; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D004247:DNA; D009353:Zinostatin