Immunoglobulin-mediated shifting of immune complexes to increased complement-dependent solubility and immunoadherence

Area of Science:

• Immunology
• Complement System
• Protein-Protein Interactions

Background:

• Investigating the role of monomeric polyclonal polyspecific IgG (mIgG) in modulating immune complex precipitation.
• Normal human serum (NHS) exhibits limited capacity to inhibit immune complex precipitation (CIICP).

Purpose of the Study:

• To determine the effect of i.v. mIgG on the CIICP capacity of NHS.
• To elucidate the mechanism underlying mIgG's influence on immune complex behavior.

Main Methods:

• Assessed CIICP of bovine serum albumin (BSA):anti-BSA (aBSA) immune complexes in NHS with varying mIgG concentrations.
• Investigated mIgG binding to immune complexes and IgG using radiolabeled mIgG (3H-mIgG).
• Evaluated mIgG's effect on complement fixation in an immune adherence hemagglutination system.

Main Results:

• mIgG dose-dependently enhanced NHS's CIICP, reaching 90% at 13.0 mg/ml.
• mIgG directly bound to immune complexes and IgG via Fab and Fc regions, with Fc binding being more significant.
• mIgG facilitated C3b fixation to immune complexes, reducing the antibody required for agglutination by 3-4 fold.

Conclusions:

• High doses of mIgG amplify complement-dependent CIICP and immune adherence hemagglutination.
• The observed effects are attributed to mIgG's interaction with antigen-reacted antibodies, enhancing complement activity.