Journal of Leukocyte Biology 45:329-335 (1989) © 1989 Alan R. Liss, inc. Effect of Interleukin 1 on the Induction and Maintenance of B Cell Tolerance In

The effects of interleukin 1 (IL-i) 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-i abrogated tolerance Induction, and when it was added at challenge phase, it also abrogated tolerance. In addition, partially purified IL-i converted TNP-HGG from a tolerogen into an immunogen without any additional exposure to antigen. Similar results were obtained when recombinant human IL-i a was used in place of partially purified natural IL-i. IL-i 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-i. Studies of IL-i production by antigen- or tolerogen-stimulated splenocytes or purified B cells showed that only antigen could elicit IL-i production in these cells. That tolerance abrogation is unique to IL-i is suggested by studies which show that TNF, 11-2, and INF y, alone, in combination with each other, or in combination with subeffective concentrations of IL-i failed to effect tolerance abro-gation. Key words: immune tolerance, cytokines, TNP-FicoI