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Speculations on the immunogenicity of self proteins.

As recombinant proteins join the physician's armamentarium to a larger and larger extent, the capacity of these "self" proteins to induce an immune response has become more widely appreciated. The most surprising observation has been that these proteins may induce an immune response even in an individual who is not deficient in the protein, but merely produces an insufficient amount for the desired biological effect. Furthermore, individuals with no apparent predisposition to auto-immunity mount antibody responses to these proteins. Fortunately, the antibody response often does not block the activity of the proteins and sometimes the response may even disappear over time. Nevertheless, the immunogenicity of human recombinant proteins is a significant limitation in their use. This review first reviews aspects of B cell tolerance and activation and then presents a model to try to explain the auto-immune response to therapeutic proteins.