Chimaeras and the Forbidden-clone Theory of Self-tolerance

Abstract

THE forbidden-clone theory of self-tolerance, which postulates that if immunologically competent cells capable of anti-self reaction arise they are soon eliminated, was widely accepted for a long time^1–3, but it has recently been challenged^4–6. Part of the challenge rests on the demonstration that a factor capable of blocking anti-self reaction is present in the serum, and part on in vitro studies indicating that cells capable of anti-self reaction occur in mice and rats. The studies with mice used chimaeras, also known as allophenic or tetraparental mice, which are made by fusing morulae of different genotypes. It is probably too early to say whether the forbidden-clone theory has been dethroned, but it may be pointed out that the studies with chimaeras are open to objection. As chimaeras may again be used for work of this nature, this objection is perhaps worth stating.