Immune complex-induced chronic and intense IL-4 independent IgG1-rheumatoid factor production in NZB mice

Immune complexes from the synovial fluid of rheumatoid arthritis (RA) patients, or artificial rheumatoid factors (RF)-like (antibody--antibody) immune complexes, induce a remarkably intense, sustained and selective immunoglobulin (Ig)G1 response under certain experimental conditions in mice. Because the IgG1 antibody response is extraordinarily strong, the role of interleukin (IL)-4, important for IgG1 synthesis, was investigated. Both C57BL/6 and NZB IL-4-deficient mice produced IgG1--RF antibodies after injection with RF-like immune complexes, although the antibody levels were slightly delayed compared to wild type mice. This shows that IL-4 is not obligatory in RF-like immune complex induced IgG1--RF production. A discrepancy in the decline of serum IgG1--RF was noted between NZB and C57Bl/6 mice. Serum IgG1-RF declined 43 days postinjection (p.i.), in C57BL/6 mice whereas high serum levels of IgG1--RF were maintained more than 100 days in the NZB mice, indicating different regulatory mechanisms in these mice. To study if the affinity for mouse IgG increased with time in NZB mice and thus become more directed against self, the cross-reactivity of the IgG1--RF antibodies with IgG from other species was investigated early and late after injection. It was, however, found that the cross-reactivity with IgG of human, goat and rabbit origin did not change between the two time points.