Effect of interleukin 1 on the induction and maintenance of B cell tolerance in vitro.
The effects of interleukin 1 (IL-1) on induction and maintenance of immune tolerance in vitro have been studied by using splenocytes from C57BL/6 male mice. B cell tolerance to the hapten trinitrophenol (TNP) was induced with TNP-human gamma globulin (HGG) and the cells were challenged with TNP-Ficoll. To determine the tolerance (or immunity), antibody concentrations in the supernatant fluids were measured by using a TNP-specific ELISA assay. Partially purified murine IL-1 abrogated tolerance induction, and when it was added at challenge phase, it also abrogated tolerance. In addition, partially purified IL-1 converted TNP-HGG from a tolerogen into an immunogen without any additional exposure to antigen. Similar results were obtained when recombinant human IL-1 alpha was used in place of partially purified natural IL-1. IL-1 is most likely acting directly on B cells rather than through the agency of T cells because purified B cells failed to become tolerant in the presence of IL-1. Studies of IL-1 production by antigen- or tolerogen-stimulated splenocytes or purified B cells showed that only antigen could elicit IL-1 production in these cells. That tolerance abrogation is unique to IL-1 is suggested by studies which show that TNF, IL-2, and INF gamma, alone, in combination with each other, or in combination with subeffective concentrations of IL-1 failed to effect tolerance abrogation.
Duan
J M
JM
Department of Pathology, State University of New York, Stony Brook 11794-8691.
Habicht
G S
GS
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D007108:Immune Tolerance / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma