The use of haptenated immunoglobulins to induce B cell tolerance in vitro. The roles of hapten density and the Fc portion of the immunoglobulin carrier

The relationship between the Fc region of trinitrophenylated (TNP)-immunoglobulins (Ig), and their ability to induce tolerance was examined. It was found that adult B cells responding to a T-independent (TI) antigen were tolerized by TNP₁₁ human gamma globulin (HGG), but not by TNP₁₀ (Fab')₂ fragments of HGG. Increasing the hapten density on the F(ab')₂ fragments overcame their inability to induce tolerance. Murine myeloma proteins of different IgG subclasses were similarly tested. A TNP₁₂-IgG2a and a TNP₁₁-IgG₁ induced tolerance, whereas two TNP_11-12-IgG3 did not. However a more heavily haptenated TNP₁₈-IgG3 was tolerogenic. These results suggest that lightly haptenated immunoglobulins depend upon Fc receptor binding to induce tolerance in adult B cells. Non-Fc receptor-binding carriers are not tolerogenic unless they are more heavily haptenated. Finally, T cell and macrophage depletion experiments suggest that the tolerogens act directly on the B cells.