The influence of Yaa on anti-DNA responses of B6-lpr mice

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Abstract

The anti-DNA autoantibody responses of mice congenic for lpr and the Y-linked autoimmune accelerator (Yaa) genes were studied to evaluate genetic interactions in murine autoimmunity. Male B6-lpr, + mice failed to generate significant anti-DNA responses in comparison to B6-+, + mice. In contrast, B6-lpr mice bearing Yaa (B6-lpr, Yaa) had markedly increased IgG anti-DNA levels in comparison to both B6-+, + and B6-lpr, + mice. To determine whether anti-DNA levels reflected the overall B-cell response to lpr and Yaa, total IgG and IgM levels were also determined. This analysis demonstrated that the increase in IgG anti-DNA produced by mice with the Yaa gene was far greater than the increase in total IgG. Taken together, these results indicate that an impaired anti-DNA response related to one gene-determined mechanism for the development of autoimmunity does not preclude the response to another. Furthermore, it appears that the polyclonal B-cell activation during murine autoimmunity may be associated with the preferential expression of certain autoantibodies.

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This work was supported by the Medical Research Service, Veterans Administration, and NIH Grants GM10356, AI08897, AI19368, and AI19010. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.

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