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..
Gandhi
R
R
Immunoendocrinology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Hussain
E
E
Das
J
J
Handa
R
R
Pal
R
R
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