PN mice spontaneously develop, with age, a lupus-like disease. The present study further evaluated autoantibody production in female PN mice. As early as 1 month of age, all PN mice had detectable IgM antibodies to dsDNA and ssDNA and two-thirds produced IgM anticardiolipin antibodies. By 3 months of age, all PN mice exhibited evidence of isotype switch in their autoantibody response; 88-100% had serum IgG antibodies to ssDNA and dsDNA, respectively. By 6-12 months of age, essentially all female PN mice had IgG antibodies to ssDNA, dsDNA, cardiolipin and other phospholipids (PS, PC, PI, and PG), and IgG and 63% produced IgG anti-mouse erythrocyte antibodies. In addition, 50-100% produced IgA antibodies to dsDNA and ssDNA, and one-third produced IgA anti-IgG antibodies. Antibodies to U1RNP and Sm were present in 81% of 6- to 12-month-old PN mice and 39-94% had IgG or IgM antibodies to mouse thymocytes. Although all four IgG isotypes were represented in the anti-dsDNA response, IgG1 antibodies dominated the IgG anticardiolipin response. The presence of IgA autoantibodies and the predominance of IgG1 in the IgG anticardiolipin response suggest that IL-4 and either IL-5 and/or TGF-beta serve as B cell stimulatory cytokines for autoreactive B cells in PN mice.