Polyreactive IgM antibodies generated from autoimmune mice and selected for histone-binding activity

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• Autoimmune diseases are characterized by the immune system attacking self-antigens.
• Histone-reactive antibodies are implicated in certain autoimmune conditions.
• Monoclonal antibodies (mAbs) are valuable tools for studying antibody characteristics.

Purpose of the Study:

• To characterize histone-reactive IgM monoclonal antibodies (mAbs) from autoimmune mice.
• To investigate the polyreactivity and V gene usage of these autoimmune mAbs.
• To compare the molecular features of autoimmune mAbs with conventional antibodies.

Main Methods:

• Generation of IgM monoclonal antibodies from spontaneously autoimmune mouse strains.
• Assessment of antibody binding to various cationic antigens and cytoskeletal proteins (polyreactivity testing).
• Analysis of immunoglobulin variable (V) gene segments and gene usage in antibody H chain third hypervariable regions.

Main Results:

• Histone-reactive IgM mAbs were successfully obtained from autoimmune mice.
• Most of these mAbs demonstrated polyreactivity, binding to multiple non-histone antigens.
• Unusual D gene segment reading frames (all three) were observed in the H chain third hypervariable regions of these autoimmune mAbs.

Conclusions:

• Autoimmune mice can produce polyreactive IgM mAbs targeting histones.
• The observed polyreactivity and unique V gene usage suggest distinct B cell selection or maturation pathways in autoimmunity.
• These findings contribute to understanding the molecular basis of autoantibody production in autoimmune diseases.