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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900579v1 183/5/3542    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Hannestad, K. Articles by Scott, H. PubMed PubMed Citation Articles by Hannestad, K. Articles by Scott, H.

The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies¹

Kristian Hannestad^2,* and Helge Scott

^* Institute of Immunology and Institute of Pathology, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway

Studies of mouse lupus models have linked the MHC H2^b haplotype with the earlier appearance of antinuclear autoantibodies and the worsening of nephritis. However, it is unknown whether H2^b by itself, in the context of pure nonlupus strains, is "silent" or sufficient with regard to loss of tolerance to chromatin (nucleosomes). In this study we show that, beginning 6–9 mo of age, H2^b-congenic BALB/c (denoted BALB.B) mice, unlike BALB/c (H2^d) and H2^k-congenic BALB/c (denoted BALB.K) mice, develop strikingly increased serum levels of anti-chromatin Ab dominated by the IgG2a subclass, along with minor increase of Abs to DNA and moderately increased total serum IgG2a. The BALB.B mice did not have glomerulonephritis or an increased mortality rate. H2^b-congenic C3H/He mice (designated C3.SW mice), unlike C3H/He (H2^k) mice, showed low but measurable serum levels of chromatin-reactive IgG2a Abs and minor but significant hypergammaglobulinemia. By immunofluorescence, IgG2a of sera from both H2^b-congenic strains stained HEp-2 cell nuclei, confirming the presence of antinuclear autoantibodies. Thus, in the context of two pure nonlupus genomes, the MHC H2^b haplotype in homozygous form is sufficient to induce loss of tolerance to chromatin.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from Helse Sør (to K.H.).

² Address correspondence and reprint requests to Dr. Kristian Hannestad, Institute for Immunology, Rikshospitalet, Sognsvannsveien 20, N-0027 Oslo, Norway. E-mail address: kristian.hannestad{at}rr-research.no

³ Abbreviations used in this paper: NZB, New Zealand Black; AHGG, aggregated human IgG; ANA, antinuclear autoantibody; AP, alkaline phosphatase; cM, centimorgan; IC, immune complex; NZW, New Zealand White; p-NPP, p-nitrophenyl phosphate.