Development of spontaneous arthritis in β2-microglobulin-deficient mice without expression of HLA-B27: Association with deficiency of endogenous major histocompatibility complex class I expression

Daniel J. Kingsbury, John P. Mear, David P. Witte, Joel D. Taurog, Derry C. Roopenian, Robert A. Colbert

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44 Scopus citations

Abstract

Objective. Mice deficient in β2-microglobulin (β2m), but expressing the human major histocompatibility complex (MHC) class I molecule HLA-B27, have been reported to develop spontaneous inflammatory arthritis (SA). We sought to determine whether, under certain conditions, β2m deficiency alone was sufficient to cause SA, and if this might be a result of class I deficiency. Methods. The following types of mice were produced: mice of the MHC b haplotype genetically deficient in β2m (β2m0) on several genetic backgrounds (C57BL/6J [B6], BALB/cJ, SJL/J, MRL/MpJ, and B6,129), mice deficient in the transporter associated with antigen processing (TAP10) on a B6,129 background, and HLA-B27-transgenic β2m0 mice on a B6 background. Cohorts were transferred from specific pathogen-free (SPF) to conventional (non-SPF) animal rooms, and evaluated clinically and histologically for the development of SA. Results. SA occurred in TAP10 and β2m0/class I-deficient mice with a mixed B6,129 genome at a frequency of 30-50%, while 10-15% of B6, SJL/J, and BALB/cJ β2m0 mice developed this arthropathy. MRL/MpJ β2m0 mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic β2m0 B6 mice compared with that in β2m0 B6 controls. Conclusion. Class I deficiency is sufficient to cause SA in mice. The frequency of disease, as well as B27-specific SA, is markedly dependent on a non-MHC genetic background. These results suggest that class I deficiency in a genetically susceptible mouse can mimic B27-associated arthropathy.

Original languageEnglish (US)
Pages (from-to)2290-2296
Number of pages7
JournalArthritis and rheumatism
Volume43
Issue number10
DOIs
StatePublished - Oct 30 2000

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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