Anti-idiotype-mediated epitope spreading and diminished phagocytosis by a human monoclonal antibody recognizing late-stage apoptotic cells.
Apoptotic cells are considered an important auto-antigenic source in diseases such as systemic lupus erythematosus (SLE). A human monoclonal antibody demonstrating exquisite specificity towards late-stage apoptotic cells was generated from an SLE patient. Polyreactive recognition of ribonucleoproteins Ro52 and Ro60 was observed. The antibody significantly diminished the phagocytosis of apoptotic cells and a concomitant decrease in transforming growth factor-beta (TGF-beta) secretion was observed. Light and heavy chain sequencing revealed the antibody to be in essentially germline configuration. Elicited anti-idiotypic antibodies bound distinct self-antigens and showed augmented reactivity towards apoptotic cells as well. Thus, near-germline encoded antibodies recognizing antigens externalized during the process of apoptosis can mediate a variety of potentially pathogenic effects; decreases in the phagocytic uptake of dying cells would constitute a disease-perpetuating event and stimulation of the idiotypic network could lead to intermolecular epitope spreading, increasing the range of molecular targets..
Immunoendocrinology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
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Gandhi
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Hussain
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J
Das
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Handa
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Pal
D000911:Antibodies, Monoclonal / Q000235:genetics; D000918:Antibody Specificity; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies; D001324:Autoantigens; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D000939:Epitopes; D006801:Humans; D007130:Immunoglobulin Idiotypes; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D016212:Transforming Growth Factor beta; D004247:DNA