Deletion of the dominant autoantigen in NZB mice with autoimmune hemolytic anemia: Effects on autoantibody and T-helper responses

Andrew M. Hall, Frank J. Ward, Chia Rui Shen, Cliff Rowe, Laura Bowie, Anne Devine, Stanislaw J. Urbaniak, Christopher J. Elson, Robert N. Barker

Research output: Contribution to journalArticle

24 Citations (Scopus)
9 Downloads (Pure)

Abstract

The mechanisms underlying apparently spontaneous autoimmune diseases, such as autoimmune hemolytic anemia (AIHA) in New Zealand Black (NZB) mice, are unknown. Here, we determine the contribution of the dominant red blood cell (RBC) autoantigen, the anion exchanger protein Band 3, to the development of NZB autoimmune responses. The approach was to prevent Band 3 expression in NZB mice by disrupting the AE1 gene. AE1-/- NZB mice produced RBC autoantibodies at the same levels as the wild-type strain, but they differed in recognizing antigens that correspond to glycophorins, rather than Band 3. Splenic T-helper (Th) cells from wild-type NZB mice proliferated strongly against multiple Band 3 peptides, particularly the dominant epitope within aa861-874. This helper response was severely attenuated in AE1-/- animals, leaving only weak proliferation to peptide aa861-874. The results demonstrate that the defect in self-tolerance in NZBAIHA is directed to the RBC type, and is not specific for, or dependent on, Band 3. However, the predisposition to RBC autoimmunity may be focused onto Band 3 by weak Th cell cross-reactivity between the helper dominant epitope and an exogenous antigen. The redundancy of the major autoantigen illustrates the requirement for specific therapy to induce dominant forms of tolerance, such as T-cell regulation.

Original languageEnglish
Pages (from-to)4511-4517
Number of pages7
JournalBlood
Volume110
Issue number13
Early online date4 Dec 2007
DOIs
Publication statusPublished - 15 Dec 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Deletion of the dominant autoantigen in NZB mice with autoimmune hemolytic anemia: Effects on autoantibody and T-helper responses'. Together they form a unique fingerprint.

  • Cite this

    Hall, A. M., Ward, F. J., Shen, C. R., Rowe, C., Bowie, L., Devine, A., Urbaniak, S. J., Elson, C. J., & Barker, R. N. (2007). Deletion of the dominant autoantigen in NZB mice with autoimmune hemolytic anemia: Effects on autoantibody and T-helper responses. Blood, 110(13), 4511-4517. https://doi.org/10.1182/blood-2007-06-094383