Elimination of autoreactive B cells in humanized SCID mouse model of SLE

Nikola S. Kerekov, Nikolina M. Mihaylova, Ivan Grozdev, Todor A. Todorov, Milena Nikolova, Marta Baleva, Maria Nikolova, Jozsef Prechl, Anna Erdei, Andrey I. Tchorbanov

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Although the exact etiology of systemic lupus erythematosus (SLE) remains elusive, B-cell hyperactivity and production of autoantibodies directed to components of the cell nucleus are a well-established pathogenetic mechanism of the disease. Therefore, the targeted inhibition of DNA-specific B cells is a logical therapeutic approach. The complement receptor type 1 (CR1, CD35) has been shown to suppress human B-cell activation and proliferation after co-cross-linking with the BCR, and may serve as a mediator for negative signal delivery. In order to evaluate this therapeutic approach in a human-like system, we used immune-restricted SCID mice transferred with PBMCs from SLE patients. The tolerance of these humanized SCID mice to native DNA was re-established after administration of a chimeric molecule consisting of a CR1-specific mAb coupled to the decapeptide DWEYSVWLSN that mimics dsDNA. The generated protein-engineered chimera was able to co-cross-link selectively native DNA-specific BCR with the B-cell inhibitory receptor CR1, thus delivering a strong inhibitory signal.

Original languageEnglish
Pages (from-to)3301-3311
Number of pages11
JournalEuropean journal of immunology
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

Keywords

  • Chimeric molecules
  • Inhibitory B-cell receptors
  • SCID models of SLE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kerekov, N. S., Mihaylova, N. M., Grozdev, I., Todorov, T. A., Nikolova, M., Baleva, M., Nikolova, M., Prechl, J., Erdei, A., & Tchorbanov, A. I. (2011). Elimination of autoreactive B cells in humanized SCID mouse model of SLE. European journal of immunology, 41(11), 3301-3311. https://doi.org/10.1002/eji.201141439