In vitro role of IL-1 in heightened IgG, anti-DNA, and nephritogenic idiotype production by B cells derived from the murine MRL/lpr lupus model.
The MRL/lpr murine model resembles human lupus both in its serologic and immunopathologic features, and is characterized by high-level IgG and autoantibody production. The precise mechanisms for this B cell hyperactivity are poorly understood. This study explored the role of IL-1 in determining high-level IgG and autoantibody production in the MRL/lpr murine lupus model by blocking IL-1 activity with a recombinant IL-1 receptor antagonist (IL-1Ra). IgG and autoantibody production (anti-DNA ab and Id-H130 activity) by B cells derived from MRL/lpr mice was significantly suppressed by treating B cell cultures with IL-1Ra. In contrast, IgG and autoantibody production by B cells derived from young MRL/lpr, MLR/++, or normal C3H/HeJ mice showed virtually no suppression with IL-1Ra. Collectively, these findings indicate that IL-1 may be an important factor in determining the heightened production of IgG, anti-DNA, and id-H130 antibody production in lupus-prone MRL/lpr mice. Furthermore, heightened IL-1 activity appears to be influenced by both age and the presence of the lpr mutation.
Singh
A K
AK
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Mao
C
C
Lebedeva
T V
TV
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D017472:Receptors, Interleukin-1 / Q000502:physiology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007375:Interleukin-1; D017472:Receptors, Interleukin-1