Inhibition of murine B1 lymphocytes by interleukin-12.
B1 cells are a subset of B lymphocytes found in many species and are implicated 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 (IL)-2, IL-4, IL-5 and IL-10. To examine further the interactions of B1 cells and Th1 cells, we have now tested the effects of the Th1 cell-inducing cytokine IL-12 on murine B1 cells. BALB/c mice were immunized with phosphorylcholine conjugated to keyhole limpet hemocyanin (PC-KLH) and simultaneously treated with 1 microgram 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 stimulation. Levels of peritoneal B lymphocytes were fully restored by day 45, but the majority of these cells belonged to the B2 subset. Additionally, proliferation of B1 cells in vitro induced by IL-5 was substantially inhibited by IL-12. IL-12 itself had no effect on viable cell recovery of peritoneal cells (PeC) cultured in vitro, but viable cell recovery was significantly decreased in PeC cultured with IL-5 plus IL-12. These results show that IL-12 causes the loss of murine peritoneal B1 cells and suggest that treatment with this cytokine may be useful for disease conditions that involve B1 cell dysfunction.
Vogel
L A
LA
Department of Microbiology, Medical College of Ohio, Toledo 43699-0008, USA.
Lester
T L
TL
Van Cleave
V H
VH
Metzger
D W
DW
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D016175:B-Lymphocyte Subsets / Q000187:drug effects*; D002478:Cells, Cultured; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C
D007166:Immunosuppressive Agents; D018664:Interleukin-12