Increased responsiveness of B. cells in the murine MRL/lpr model of lupus nephritis to interleukin-1 beta.

Abstract

The high-level production of immunoglobulin G (IgG), anti-DNA antibodies, and id-H130-expressing antibodies has been correlated with both the presence and the severity of nephritis in the murine MRL/lpr lupus model. Although evidence suggests that interleukin-1 (IL-1) could be an important factor in the immunopathogenesis of murine lupus nephritis, its influence on B cell hyperactivity is poorly understood. The in vitro responsiveness of B cells derived from lupus-prone old and young MRL/lpr and healthy C3H/HeJ mice to exogenous IL-1 beta was examined. B cells derived from MRL/lpr mice, and particularly old MRL/lpr mice, were hyperresponsive to exogenous IL-1 beta, demonstrating a marked increase in IgG production with 50 pg/mL concentrations of IL-1 beta as compared with control medium. Whereas MRL/lpr B cells demonstrated remarkable unresponsiveness to high concentrations of IL-1 beta. By contrast, B cells derived from C3H/HeJ mice and cultured with IL-1 beta showed virtually no alteration in IgG production. In addition, B cells derived from old MRL/lpr mice and cultured with IL-1 beta showed a significant increase in the production of anti-DNA and id-H130-expressing antibodies. Collectively, these observations demonstrate increased B cell responsiveness to exogenous IL-1 beta and suggest that heightened IL-1 bioactivity in the murine MRL/lpr lupus model may influence high-level IgG and autoantibody production.