Critical self-epitopes are key to the understanding of self-tolerance and autoimmunity

✍ Scribed by Guillermo Dighiero; Noel R Rose

• Publisher: Elsevier Science
• Year: 1999
• Tongue: English
• Weight: 197 KB
• Volume: 20
• Category: Article
• ISSN: 0167-5699
• DOI: 10.1016/s0167-5699(99)01509-1

✦ Synopsis

n the early 1900s, controversies between the Ehrlich school and the Metchnikoff school of immunology laid the foundation for our current notions of self-tolerance and autoimmunity. The experiments of Ehrlich and Morgenroth showed that animals did not produce autoantibodies to their own erythrocytes 1,2 . Indeed, these seminal observations still underlie our everyday practice of blood transfusion. For example, individuals of blood group A never produce anti-A antibodies and blood group B individuals do not produce anti-B antibodies, as demonstrated clearly by Landsteiner 3 . In contrast, Metchnikoff's group established the reality of autoimmunization by demonstrating the presence of autoantibodies, either under normal conditions or after immunization 4,5 . These findings appeared to contradict directly the concept of horror autotoxicus formulated by Ehrlich, and the rules of blood group compatibility.

Considerable progress has been achieved in recent years in refining our understanding of self-tolerance and autoimmunity through the investigation of natural autoantibodies and the advent of transgenic mouse models. This new and interesting evidence needs to be reconciled with the lessons learned from the studies on red blood cell antigens, because these models have provided very solid and consistent data on the rules underlying self-tolerance. This review, restricted mainly to B-cell tolerance, aims to integrate the earlier evidence based upon Ehrlich's and Metchnikoff's pioneering investigations with recent findings suggesting that autoimmunization is a physiological event.