Increased responsiveness of B. cells in the murine MRL/lpr model of lupus nephritis to interleukin-1 beta.
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.
Lebedeva
T V
TV
New England Medical Center, Department of Medicine, Boston, MA 02111.
Singh
A K
AK
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007375:Interleukin-1 / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007375:Interleukin-1; D004247:DNA