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

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.