Prolonged inhibition of IgE production in mice following treatment with an IgE-specific immunotoxin

Abstract

The synthesis of IgE antibodies by B cells is the first in a series of steps resulting in an allergic response. To eliminate IgE-bearing B cells and thereby prevent IgE production, we have developed an immunotoxin (ITA) composed of the non-anaphylactic 84.1c anti-mouse IgE mAb and the A chain of ricin (ricin A). This ITA specifically inhibited the induction of IgE synthesis by lipopolysaccharide plus interleukin-4 (LPS+IL-4) in vitro, and antigen-specific IgE production in vivo in adult mice. A single dose of anti-IgE ITA, given within a week (either before or after) of antigen challenge completely abolished antigen-specific primary IgE responses. No IgE production was seen for 2 months after ITA treatment. Following antigenic re-challenge, a suppressed secondary response (over 50% reduction) was still seen in the ITA-treated mice, 100 days after immunization. The results of this study demonstrate the potential use of anti-IgE toxin conjugates for the suppression of periodic (seasonal) allergic outbreaks.