Interleukin-1 contributes to high level IgG production in the murine MRL/lpr lupus model.
The autoimmune syndrome in MRL/lpr mice resembles human lupus, both in its serologic and immunopathologic characteristics. The contribution of IL-1 to high-level Ig production in the MRL/lpr model is poorly understood. We investigated the effect of treating B-cell-enriched, or, B plus T cell suspensions derived from either pre-disease or diseased lupus-prone MRL/lpr mice with IL-1 beta or IL-1 receptor antagonist (IL-1Ra). Disparate patterns of IgG production by B cells and B plus T cells derived from diseased versus pre-diseased MRL/lpr mice was observed following treatment with IL-1 beta. Remarkably, IL-1 beta caused significant suppression in IgG production by B cells derived from diseased MRL/lpr mice as compared to B cells derived from pre-disease mice. In mix-and-match experiments with B plus T cells from pre-disease and diseased MRL/lpr mice, both T cell help and B cell hyperactivity, originating in diseased MRL/lpr mice were found to be important factors in high-level IgG production in diseased MRL/lpr mice. Furthermore, IL-1Ra treatment of B plus T cell co-cultures derived from diseased MRL/lpr mice was able to significantly suppress IgG production, whereas, IL-1Ra treatment of B plus T cell co-cultures derived from pre-disease MRL/lpr mice demonstrated virtually no suppression in IgG production. Collectively, these results indicate a potentially important but complex role for IL-1 in influencing high-level IgG production in MRL/lpr mice with established disease.
Singh
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AK
Department of Medicine (Nephrology), New England Medical Center, Boston, MA 02111.
Lebedeva
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TV
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000096:biosynthesis*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012795:Sialoglycoproteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins