What is the Role of Natural Autoantibodies (NAb) in Health and Disease?

I. Antikeratin antibodies enhance the elimination of keratin after keratinocyte death.

II. IgG NAb anti-band 3 proteins participate in the elimination of senescent red blood cells.

III. IgM NAb increase resistance to tumors.

IV. NAb may be cytotoxic.

V. NAb may inhibit interferon action by binding to the cell surface.

VI. NAb may inhibit NK cell activity.

VII. IgM NAb anti-IgG inhibits the binding of IgG to self-antigens.

VIII. NAb anti-idiotype antibodies to pathogenic autoantibodies may have therapeutic potential.

IX. Some NAb posess proteolytic activity on the vasoactive intestinal peptide.

X. IgM (but not IgG) NAb enhance phagocytosis of parasites.

XI. Natural anti-trinitrophenyl autoantibodies protect against viral infection.

Yet the appearance of normal auto antibodies is a carefully controlled event. Autoimmune disorders might simply arise as a consequence of the dysregulation of natural physiological autoimmunity.

The mechanisms involved in the shift from physiological to pathological autoimmunity are unknown.

Several theories have been proposed since the mid-twentieth century to explain origin of self tolerance but the exact mechanism of induction and maintenance of tolerance is not fully understood.