Immunological responsiveness of neonatal A/J mice to isotypic determinants of syngeneic IgE.

Abstract

We have previously shown that adult A/J mice produce high titers of anti-IgE with isotypic or idiotypic specificities in response to challenge with a conjugate of KLH with syngeneic monoclonal IgE. Thus, B cells that can synthesize anti-IgE are present in the mice. Adult mice are unresponsive to unconjugated IgE in CFA, suggesting that tolerance exists at the level of T cells. The present study shows that neonatal mice produce anti-IgE antibodies in response to unconjugated IgE in CFA, but that this capacity is lost after the age of 2-3 wk. The loss of responsiveness corresponds closely with the appearance of detectable IgE in serum, suggesting that the IgE may induce tolerance. The affinities of anti-IgE antibodies produced by neonatal mice fall in the range of values obtained with KLH-IgE in adult mice. Tolerance to unconjugated IgE in CFA can be induced in neonatal mice by administration of IgE in saline. In addition, the tolerant state can be induced by adoptive transfer of spleen cells from adult mice. The time-dependent acquisition of tolerance provides a useful model for studying mechanisms of tolerance and autoimmunity.

IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE.

“…We demonstrated that this is accompanied by profound decreases in the level of serum IgE and the number of IgEsecreting cells in the spleen (4,5 When IgE is inoculated in saline on the day of birth, it fails to elicit anti-IgE antibodies and renders mice tolerant to IgE inoculated on day 9 or 10 (that would otherwise have caused the synthesis of anti-IgE) (4). Tolerance to a challenge on day 9 can similarly be induced by inoculations of small (0.25 ,g) doses of IgE on days 3, 5, and 7; larger amounts of IgE (_5 ,ug) are immunogenic rather than tolerogenic when inoculated on these days (8,9).…”

“…Alternatively, mice can be tolerized against a challenge with IgE on day 9 or 10 by inoculation of 5 x 106 syngeneic adult splenic B cells, but not T cells, on the day of birth (4,8). B cells from 9-day-old mice, which lack detectable serum IgE, are not tolerogenic (8).…”

“…The unexpected, very early secretion of IgE in the thymus may provide a potent tolerogenic signal to developing T cells. (CRI-) and SE20.2 (CRI)) are of A/J derivation and are specific for p-azobenzenearsonate; each mAb was affinitypurified (4). Radioimmunoassays for Mouse Anti-IgE and for Serum IgE.…”

Role of antibody and T cells in the long-term inhibition of IgE synthesis.

“…inhibition of subsequent IgE synthesis was found to correspond closely with the period when anti-IgE antibodies can be induced by immunization with unconjugated IgE (2,4). The inference we drew, that anti-IgE antibodies are responsible at least in part for the inhibition of IgE synthesis, was supported by the observation that syngeneic anti-IgE, passively administered to 4-to 8-week-old mice, can profoundly inhibit total and specific IgE synthesis in response to a subsequent challenge with antigen (3).…”

“…Unconjugated IgE is not immunogenic in adult mice, which suggests that the KLH is needed to provide the required T-cell help (1). Unconjugated syngeneic IgE can, however, induce anti-IgE antibody formation if inoculated in amounts of .2.5 ,g after the day of birth but before the age of 10 days; the IgE is immunogenic when inoculated either in complete Freund's adjuvant (CFA) or in saline (2,3). The loss of ability to respond to unconjugated IgE corresponds closely with the age at the first appearance of IgE-secreting cells in lymphoid tissue; they are first detectable in the thymus between the ages of 7 and 11 days and soon afterwards in lymph nodes and spleen (4).…”