Lack of requirement for cell cooperation in the antibody response to DNP conjugated to levan.

The cellular basis of the antibody response to dinitrophenylated levan (DNP-LE) was investigated using a combination of in vivo and in vitro techniques. The results indicated that the induction of the primary response to DNP-LE is independent of the function of macrophages or T cells. However, these cells may regulate the response to DNP-LE (as for other T-independent antigens), as suggested by the prolongation of the response by adjuvants. No evidence of collaboration between carrier (LE)-reactive and hapten (DNP)-reactive B cells in the induction of the response to DNP-LE was obtained (either by inducing tolerance to LE (in vivo or in vitro) or culturing in the presence of excess LE). Thus DNP-LE, like other thymus-independent antigens (e.g., DNP-polymerized flagellin, DNP-Ficoll) may trigger B cells directly. © 1975

Role of epitope density in the induction of tolerance and immunity with thymus-independent antigens. III. Interaction of epitope density and receptor avidity.

The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectly by a plaque inhibition assay) was investigated. It was found that high avidity precursors (IgG) were tolerized by antigen of much lower epitope density, and at lower concentration, than were low avidity precursors (especially IgM cells). IgA cells were intermediate in behavior. These results suggest that the epitope density effect acts by ensuring a necessary degree and/or energy of antigen binding

Comparison of in vitro immunogenicity, tolerogenicity and mitogenicity of dinitrophenyl-levan conjugates with varying epitope density.

The mitogenicity, immunogenicity and tolerogenicity of various DNP-levan (DNP-LE) conjugates were compared using in vitro methods. Anti-DNP antibody synthesis induced by DNP-LE conjugates was related to the epitope density of DNP, BUT WAS NOT AFFECTED BY Macrophage dependent and was not influenced by the degree of hapten conjugation. These results imply that mitogenicity of an antigen is not necessarily related to the specific triggering of B cells

Lack of requirement for cell cooperation in the antibody response to DNP conjugated to levan.

The cellular basis of the antibody response to dinitrophenylated levan (DNP-LE) was investigated using a combination of in vivo and in vitro techniques. The results indicated that the induction of the primary response to DNP-LE is independent of the function of macrophages or T cells. However, these cells may regulate the response to DNP-LE (as for other T-independent antigens), as suggested by the prolongation of the response by adjuvants. No evidence of collaboration between carrier (LE)-reactive and hapten (DNP)-reactive B cells in the induction of the response to DNP-LE was obtained (either by inducing tolerance to LE (in vivo or in vitro) or culturing in the presence of excess LE). Thus DNP-LE, like other thymus-independent antigens (e.g., DNP-polymerized flagellin, DNP-Ficoll) may trigger B cells directly. © 1975

Role of epitope density in the induction of tolerance and immunity with thymus-independent antigens. Iii. Interaction of epitope density and receptor avidity.

The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectly by a plaque inhibition assay) was investigated. It was found that high avidity precursors (IgG) were tolerized by antigen of much lower epitope density, and at lower concentration, than were low avidity precursors (especially IgM cells). IgA cells were intermediate in behavior. These results suggest that the epitope density effect acts by ensuring a necessary degree and/or energy of antigen binding

Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. I. Studies with 2,4-dinitrophenyl conjugates in vitro.

The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance