Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an auto-antigen, histone H3.

Abstract

BACKGROUND:

NC/Nga mice are known to show a spontaneous outbreak of atopic-like dermatitis accompanied by a marked elevation in serum IgE levels when reared in a conventional environment. The specific effects of such a strong serum IgE response on the development of the dermatitis and specific antigens recognized by the IgE antibodies are still uncertain.

OBJECTIVE AND METHODS:

To characterize the IgE of NC/Nga mice, we established IgE-secreting hybridoma clones from spleen cells of NC/Nga mice spontaneously developing dermatitis and identified variable-region genes and specific antigens of the IgE monoclonal antibodies (mAbs). Serum polyclonal IgE, as well as IgG1 and IgG2a, specific for the identified antigen were also analysed.

RESULTS:

Four IgE-producing hybridoma clones were established. Variable-region nucleotide sequences of the IgE mAbs showed that these clones did not necessarily share common germline gene segments (V, D or J) for each variable region, and several somatic mutations had occurred in the V gene segments. Through antigen screening, histone H3 was identified to be an auto-antigen recognized by three of the four IgE mAbs. Serum IgE as well as IgG1 specific for histone H3 were almost undetectable in 6-week-old mice, but rapidly increased by 10-12 weeks of age. This age-dependent increase in the serum anti-histone H3 IgE was roughly in parallel with the onset of dermatitis, and slightly preceding total IgE elevation. The serum-specific IgE level correlated well with a dermatitis-severity score of each mouse at 12-16 weeks of age, and weakly with the severity of ear erosion of each mouse over 28 weeks of age. Furthermore, immunologically detectable histone-H3 antigens were observed in skin tissue sections from the dermatitis sites.

CONCLUSION:

In NC/Nga mice, anti-histone H3 auto-antibodies may contribute, at least in part, to the considerably elevated serum IgE and might play some roles in the development and exacerbation of dermatitis.

• Authors: T Matsubara, N Aoki, S Hino, T Okajima, D Nadano, T Matsuda
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 39 Issue 4 Pg. 579-90 (Apr 2009) ISSN: 1365-2222 [Electronic] England
• PMID: 19226275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Autoantibodies
• Autoantigens
• Histones
• Immunoglobulin E

Topics

• Age Factors
• Animals
• Antibodies, Monoclonal (immunology)
• Autoantibodies (blood, immunology)
• Autoantigens (immunology)
• Dermatitis, Atopic (immunology, pathology)
• Disease Models, Animal
• Female
• Histones (immunology)
• Hybridomas
• Immunoglobulin E (blood)
• Mice
• Mice, Inbred Strains
• Skin (immunology, pathology)