DIRECT BINDING OF IL-12 TO HUMAN AND MURINE B-LYMPHOCYTES

IL-12 has been shown to play a central role in cell-mediated inflammat ory reactions through direct activation of T cells and NK cells. IL-12 also strongly influences humoral immunity but these effects have been thought to be indirect and caused by intermediary cytokines, Using fl ow cytometry, we now show that IL-12 directly interacts with B cells. Freshly isolated murine peritoneal B-1 and conventional a lymphocytes bound IL-12, but splenic a cells failed to react unless first stimulat ed with lipopolysaccharide. All murine a cell sources were found to ex press IL-12R beta 1 subunit transcripts as detected by PCR and RNase p rotection assays. IL-12 binding was also detected on phytohemagglutini n-stimulated human T cell blasts and Staphylococcus aureus/IL-2-stimul ated a cell blasts but not on freshly isolated peripheral blood lympho cytes. Similarly, IL-12 directly bound to the human SKW6,4 Burkitt's B cell lymphoma line. In all cases positive staining was ablated by omi tting IL-12 from the procedure, showing that it was not due to detecti on of endogenous IL-12, These findings indicate that a cells represent another major target for IL-12 in addition to T and NK cells, and tha t IL-12 can directly affect humoral immunity.