The origin of autoantibodies

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• Autoantibodies (autoAb) are hallmarks of autoimmune diseases but are also found in healthy individuals.
• The origin and function of autoAb in normal physiology and disease remain incompletely understood.

Purpose of the Study:

• To investigate the characteristics of monoclonal autoantibodies (m-autoAb) from normal individuals and patients with autoimmune diseases.
• To explore the potential role of natural autoAb in the pathogenesis of autoimmunity.

Main Methods:

• Hybridoma technology was used to generate monoclonal autoantibodies (m-autoAb) from lymphocytes of unimmunized normal mice and healthy humans.
• Analysis of m-autoAb included binding specificity, isotype, and idiotype characterization.
• Comparison of autoAb from normal individuals and patients with systemic lupus erythematosus (SLE) and other autoimmune conditions.

Main Results:

• Many m-autoAb from normal sources exhibited polyspecific binding to multiple self-antigens and shared a common cross-reactive idiotype (CRI).
• Low levels of autoAb with similar binding patterns and idiotypes are continuously present in healthy individuals.
• AutoAb from patients with SLE and other autoimmune diseases showed similar polyspecificity, IgM isotype, and CRI, which were nearly identical to those in natural autoAb from normals.

Conclusions:

• Lymphocytes producing autoAb are a common component of the normal B cell repertoire.
• The findings suggest that natural autoAb may play a role in the pathogenesis of autoimmune diseases, particularly in conditions like SLE.
• Further research is needed to understand the function, regulation, and in vivo activation of autoAb, and the influence of factors like viruses on autoantibody production and autoimmunity.