Autoantibody production and cytokine profiles of MHC class I (β2- microglobulin) gene deleted New Zealand Black (NZB) mice

Shao Yuan Chen, Yuichi Takeoka, Larry Pike-Nobile, Aftab A. Ansari, Richard Boyd, M. Eric Gershwin

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

We established a colony of MHC class I deleted (knockout) NZB mice, which lack the β2 microglobulin gene (NZB.β2m(-/-)), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33+ cells, a marker of premature thymocyte maturation, was also seen in NZB.β2m(-/-). However, although NZB.β2m(-/-) mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.β2m(-/-) had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P- driven levels of IFN-γ, IL-4, IL-6, and IL-12 in cells from NZB, NZB.β2/(- /-), and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-γ, and a marked increase in IL-6 and IL-12 in NZB and NZB.β2m(-/-) mice.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalClinical Immunology and Immunopathology
Volume84
Issue number3
DOIs
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pathology and Forensic Medicine

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