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.