FIGURE 7.

Immunization with β₂GPI in the presence of LPS induces a spread of the immune response that recapitulates the sequence of autoantibody emergence in human SLE. C57BL/6 or BALB/c mice were immunized with soluble Ag (HEPES buffer, LPS, or human β₂GPI in the absence or presence of LPS), as in Fig. 6. The kinetics of the response are shown for mice immunized with human β₂GPI in the presence of LPS. A, Diluted (1/100) serum or plasma of the immunized mice was evaluated in duplicate for IgG Ab to β₂GPI, CL, Ro/SS-A (Ro), La/SS-B (La), dsDNA, nRNP, and Sm by ELISA following the first through fourth immunization. Data represent the mean OD₄₀₅ ± SE for each group of mice (n = 10) with error bars, and 2.75 represents the maximal OD₄₀₅ value. Data shown without SE indicate that all mice in that group had maximal OD₄₀₅ values. The SLE-related autoantibodies emerged in the following sequence: anti-β₂GPI, aCL, anti-Ro/SS-A and anti-La/SS-B, anti-dsDNA, anti-nRNP, and anti-Sm. Basically, they fall into three sequential groups (grouped by brackets): 1) anti-β₂GPI and aCL Abs (aPL) (filled symbols); 2) anti-Ro/SS-A, anti-La/SS-B, and anti-dsDNA (grayed symbols); and 3) anti-nRNP and anti-Sm (open symbols). B, The percentage (%) of C57BL/6 and BALB/c mice positive for each of the SLE-related IgG autoantibodies following the first through fourth immunization with β₂GPI in the presence of LPS. Autoantibody positivity for duplicate serum samples assayed by ELISA was defined as a mean OD₄₀₅ ≥ 0.25. C57BL/6 and BALB/c mice show a similar sequence of autoantibody emergence, but SLE-related autoantibodies emerged earlier in the C57BL/6 mice. These data are representative of three independent experiments (n = 10 mice per group).