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


Tsukasa Matsuda, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.


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 occured 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.