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Activation of rat complement by soluble and insoluble rat IgA immune complexes
M Rits1, P S Hiemstra, H Bazin
1International Institute of Cellular and Molecular Pathology, University of Louvain, Brussels, Belgium.
European Journal of Immunology
|December 1, 1988
Summary
Rat immunoglobulin A (IgA) immune complexes activate the complement system via the alternative pathway. Polymerization and size of IgA immune complexes significantly influence complement activation efficiency.
Area of Science:
- Immunology
- Complement System
- Antibody Function
Background:
- Immunoglobulin A (IgA) plays a crucial role in mucosal immunity.
- The ability of IgA to activate the complement system, particularly the alternative pathway, is not fully understood.
- Investigating IgA's complement-activating potential is vital for understanding immune responses.
Purpose of the Study:
- To investigate the capacity of rat monoclonal IgA to activate the rat complement (C) system.
- To determine the influence of IgA aggregation state (monomeric, dimeric, polymeric) and immune complex formation on C activation.
- To elucidate the role of IgA in the assembly of the terminal membrane attack complex.
Main Methods:
- Coating IgA onto a solid phase and assessing C3 binding in normal rat serum (NRS) with Mg-EGTA.
- Preparing and assessing soluble and insoluble rat IgA immune complexes (ICs) for C activation and consumption.
- Analyzing C activation by IgA ICs using gel filtration and antibody/antigen ratios.
- Demonstrating terminal membrane attack complex assembly via lysis of trinitrophenyl-conjugated rat red blood cells (TNP-RRBCs).
Main Results:
- Dimeric, polymeric, and secretory rat IgA bound C3, unlike monomeric IgA or mouse IgA.
- Insoluble IgA ICs, particularly polymeric IgA, activated the alternative pathway of rat C, with polymeric IgA being four times more efficient than monomeric.
- Soluble dimeric IgA ICs activated C, with high-molecular-weight ICs being more efficient than low-molecular-weight ones.
- IgA-coated TNP-RRBCs induced lysis, indicating terminal C complex formation.
Conclusions:
- Rat IgA, particularly in aggregated or complexed forms, effectively activates the alternative pathway of the homologous complement system.
- The efficiency of complement activation by IgA ICs is dependent on their size and the degree of IgA polymerization.
- These findings highlight IgA's significant role in complement-mediated immune responses.