HAPTEN-SPECIFIC IGE ANTIBODY-RESPONSES IN MICE .7. CONVERSION OF IGE NON-RESPONDER STRAINS TO IGE RESPONDERS BY ELIMINATION OF SUPPRESSOR-T CELL ACTIVITY

Abstract

Mice of the inbred strains SJL (H-2s) and AKR (H-2k) are non-responders and low-responders, respectively, in terms of their capacity to develop antibody responses of the IgE [immunoglobulin E] class when immunized with conventional proteins and hapten-protein conjugates under conditions optimal for eliciting IgE responses in high-responder mice, such as BALB/c (H-2d), to these same antigens. BALB/c mice preimmunized with ASC [Ascaris suum extract] and then challenged 7 days later with DNP[dinitrophenylated]-ASC develop peak augmented primary IgE anti-DNP antibody responses of 320 PCA [passive cutaneous anaphylaxis] units; SJL and AKR mice develop responses which are 16-fold and 4-fold lower, respectively. Pretreatment of the latter 2 strains with appropriate doses of x-irradiation (150 R), cyclophosphamide (100 mg/kg) or ALS [anti-lymphocyte serum] (150 .mu.l) before carrier-preimmunization strikingly enhances the magnitude of IgE antibody responses in such mice to levels as high as 64-fold above those of untreated control mice of the same strains. The capacity of such maneuvers to convert poor IgE responders to high responder status reflects elimination of nonantigen-specific suppressor T [thymus-derived] lymphocytes which are naturally present and normally function to suppress or dampen the IgE antibody response in a relatively selective manner. It appears that these cells modulate IgE responses by acting at least at 2 distinct points. The most effective activity seems to be at the level of induction of carrier-specific helper T cells. A 2nd locus of inhibitory activity is more distal in the response, impeding helper T cell-B [bone marrow-derived] cell cooperative interactions or suppressing B cell differentiation and/or function directly. The state of poor responsiveness of the SJL and AKR strains for the IgE antibody class is apparently not a reflection of a genetic inability to develop IgE responses but rather a manifestation of a genetic capability to actively inhibit IgE antibody synthesis.