B cells regulate CD40 ligand-induced IL-12 production in antigen-presenting cells (APC) during T cell/APC interactions.
Although stimulation of freshly isolated murine spleen cells with anti-CD3 mAb or Con A failed to generate IL-12 production, the same cell preparations depleted of B cells produced IL-12. Addition of normal B cells inhibited IL-12 production in a cell number-dependent manner. IL-12 production was dependent on the presence of CD4+, but not of CD8+, T cells, and inhibited by addition of anti-CD40 ligand (CD40L) mAb. Anti-CD3 or Con A stimulation induced CD40L expression only on CD4+ T cells, which was inhibited in the presence of B cells. IL-12 production was also induced by interactions between CD40L-transfected Chinese hamster ovary cells and splenocytes depleted of T and B cells, but not of APC, indicating CD40L-induced IL-12 production by APC. The involvement of CD40 molecules was examined by comparing the ability of cells from CD40-deficient (CD40 -/-) and wild-type mice (CD40 +/+) to produce IL-12. Spleen cells from CD40 -/- and CD40 +/+ mice produced comparable amounts of IL-12 in response to bacterial stimuli. However, the B cell-depleted fraction from CD40 -/- mice failed to produce IL-12 when stimulated with anti-CD3 or Con A or when cocultured with CD40L-expressing Chinese hamster ovary cells. These results indicate that CD40L expressed on activated T cells induces APC to produce IL-12 through CD40/CD40L interaction, but this pathway is competitively inhibited by CD40+ B cells incapable of producing IL-12 upon stimulation with CD40L. Thus, this might represent a novel mechanism underlying the regulation of cell-mediated and humoral immunity.
Maruo
S
S
Biomedical Research Center, Osaka University Medical School, Japan.
Oh-hora
M
M
Ahn
H J
HJ
Ono
S
S
Wysocka
M
M
Kaneko
Y
Y
Yagita
H
H
Okumura
K
K
Kikutani
H
H
Kishimoto
T
T
Kobayashi
M
M
Hamaoka
T
T
Trinchieri
G
G
Fujiwara
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D023201:CD40 Ligand; D002448:Cell Adhesion / Q000276:immunology; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008024:Ligands; D008562:Membrane Glycoproteins; D003208:Concanavalin A; D023201:CD40 Ligand; D018664:Interleukin-12