INHIBITION OF MURINE B1 LYMPHOCYTES BY INTERLEUKIN-12

B1 cells are a subset of B lymphocytes found in many species and are i mplicated in the development of autoimmunity. B1 cells have previously been shown to be suppressed by the T helper (Th)1 cytokine interferon (IFN)-gamma, and to be stimulated by the Th2 cytokines interleukin (I L)-2, IL-4, IL-5 and IL-10. To examine further the interactions of B1 cells and Th 1 cells, we have now tested the effects of the Th I cell- inducing cytokine IL-12 on murine B1 cells. BALB/c mice were immunized with phosphorylcholine conjugated to keyhole limper hemocyanin (PC-KL H) and simultaneously treated with 1 mu g recombinant murine IL-12 for 3 consecutive days. in addition to altering the isotype and idiotype distribution of anti-PC antibodies, IL-12 treatment was found to cause a loss of peritoneal, but not splenic B lymphocytes in immunized mice . B cell depletion required exposure to IL-12 plus antigenic stimulati on. Levels of peritoneal B lymphocytes were fully restored by day 45, but the majority of these cells belonged to the B2 subset. Additionall y, proliferation of B1 cells in vitro induced by IL-5 was substantiall y inhibited by IL-12. IL-12 itself had no effect on viable cell recove ry of peritoneal cells (PeC) cultured in vitro, but viable cell recove ry was significantly decreased in PeC cultured with IL-5 plus IL-12. T hese results show that IL-12 causes the loss of murine peritoneal B1 c ells and suggest that treatment with this cytokine may be useful for d isease conditions that involve B1 cell dysfunction.