Direct binding of IL-12 to human and murine B lymphocytes.
IL-12 has been shown to play a central role in cell-mediated inflammatory 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 flow cytometry, we now show that IL-12 directly interacts with B cells. Freshly isolated murine peritoneal B-1 and conventional B lymphocytes bound IL-12, but splenic B cells failed to react unless first stimulated with lipopolysaccharide. All murine B cell sources were found to express IL-12R beta 1 subunit transcripts as detected by PCR and RNase protection assays. IL-12 binding was also detected on phytohemagglutinin-stimulated human T cell blasts and Staphylococcus aureusl IL-2-stimulated B cell blasts but not on freshly isolated peripheral blood lymphocytes. Similarly, IL-12 directly bound to the human SKW6.4 Burkitt's B cell lymphoma line. In all cases positive staining was ablated by omitting IL-12 from the procedure, showing that it was not due to detection of endogenous IL-12. These findings indicate that B cells represent another major target for IL-12 in addition to T and NK cells, and that IL-12 can directly affect humoral immunity.
Vogel
L A
LA
Department of Microbiology and immunology, Medical College of Ohio, Toledo 43699-0008, USA.
Showe
L C
LC
Lester
T L
TL
McNutt
R M
RM
Van Cleave
V H
VH
Metzger
D W
DW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002051:Burkitt Lymphoma; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding / Q000276:immunology; D018123:Receptors, Interleukin / Q000032:analysis; D053707:Receptors, Interleukin-12; D014407:Tumor Cells, Cultured
D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12