Large numbers of cells in normal mice produce antibody components of isologous erythrocytes

Abstract

THERE are a number of arguments against the idea¹ that self-tolerance depends on a purge of all self-reactive clones early in development. First, antigens which appear later in development, for example, Ig idiotypes, must induce tolerance to themselves. Second, autoimmune diseases are often reversible, implying that when anti-self-reactive cells arise late, they may still be controlled. Third, the recent finding (refs 2–4 and L. M. Pilarski and A.J.C., unpublished) that single clones of antibody-forming cells rapidly produce variants also implies a continuous monitoring and control of immunocompetent cells. Self-reactive variants must arise during many immune responses, and must normally be prevented from causing autoimmune disease. Fourth, the distinction between anti-self and anti-not-self specificities is obviously not clear-cut. Given the great diversity of self components in mammals, it is probable that almost any antibody will react to some self antigens with low affinity.