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Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an auto-antigen, histone H3.
Clin Exp Allergy. 2009 Apr; 39(4):579-90.CE

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+Show Affiliations

Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19226275

Citation

Matsubara, T, et al. "Serum and Monoclonal Immunoglobulin E Antibodies From NC/Nga Mice With Severe Atopic-like Dermatitis Recognize an Auto-antigen, Histone H3." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 39, no. 4, 2009, pp. 579-90.
Matsubara T, Aoki N, Hino S, et al. Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an auto-antigen, histone H3. Clin Exp Allergy. 2009;39(4):579-90.
Matsubara, T., Aoki, N., Hino, S., Okajima, T., Nadano, D., & Matsuda, T. (2009). Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an auto-antigen, histone H3. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 39(4), 579-90. https://doi.org/10.1111/j.1365-2222.2008.03174.x
Matsubara T, et al. Serum and Monoclonal Immunoglobulin E Antibodies From NC/Nga Mice With Severe Atopic-like Dermatitis Recognize an Auto-antigen, Histone H3. Clin Exp Allergy. 2009;39(4):579-90. PubMed PMID: 19226275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic-like dermatitis recognize an auto-antigen, histone H3. AU - Matsubara,T, AU - Aoki,N, AU - Hino,S, AU - Okajima,T, AU - Nadano,D, AU - Matsuda,T, Y1 - 2009/02/10/ PY - 2009/2/20/entrez PY - 2009/2/20/pubmed PY - 2009/5/27/medline SP - 579 EP - 90 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin Exp Allergy VL - 39 IS - 4 N2 - 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. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/19226275/Serum_and_monoclonal_immunoglobulin_E_antibodies_from_NC/Nga_mice_with_severe_atopic_like_dermatitis_recognize_an_auto_antigen_histone_H3_ L2 - https://doi.org/10.1111/j.1365-2222.2008.03174.x DB - PRIME DP - Unbound Medicine ER -