Enhancement of antigen-induced interleukin 4 and IgE production by specific IgG₁ in murine lymphocytes

Conalbumin (CA)-specific type 2 helper T cell (Th2) clone, D10G4.1 (D10) produces IL4 when stimulated with varying doses of TNP-CA in the presence of mitomycin C-treated C3H spleen cells or purified B cells as antigen-presenting cells (APC). The production of IL4 was assessed by bioassay and by expression of IL4 mRNA. IL4 production reached maximum at 100 μg/ml of TNP-CA, whereas 1 μg/ml of the antigen induced less than 10% of the maximum level of IL4. This lower level of IL4 production was augmented to the maximum level when monoclonal anti-TNP IgG₁, was added to the culture at 0.5-1 μg/ml. Anti-TNP IgE, but not anti-TNP IgM, was also effective, though IgE was 1 10 as effective as IgG₁. IgG₁ with an irrelevant specificity and F(ab')₂ of anti-TNP IgG₁ did not show augmenting effects. Moreover, the enhancement by anti-TNP IgG₁ was completely abolished by monoclonal antibody against murine FcγRII, 2.4G2. These results suggest that a low dose of the antigen complexed with IgG₁ is focused on APC by means of FcγRII, processed, and presented efficiently to the Th2 clone. On the other hand, the co-culture of D10 with normal C3H B cells in the presence of 1-100 μg/ml TNP-CA resulted in polyclonal IgE production. Anti-TNP IgG₁ markedly augmented the lower level of IgE production induced by a suboptimal dose of the antigen (1 μg/ml). This augmentation was shown to be dependent on endogenous IL4 because the enhancement was abolished by monoclonal anti-IL4 (11B11).