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.