1. ¹Immunoendocrinology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
2. ²Department of Biosciences, Jamia Millia Islamia, Maulana Mohammed Ali Jauhar Marg, New Delhi, India
3. ³Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

Correspondence: R Pal, Immunoendocrinology Lab, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi. Tel: +91 11 26703787; Fax: +91 11 26162125; E-mail: rahul@nii.res.in

Received 8 March 2005; Revised 5 December 2005; Accepted 21 December 2005; Published online 10 February 2006.

Abstract

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- (TGF-) 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.