Mechanism of immunoglobulin A polymerization

Area of Science:

• Immunology
• Molecular Biology
• Protein Chemistry

Background:

• Polymeric immunoglobulin A (IgA) plays a crucial role in mucosal immunity.
• Understanding the quaternary structure of IgA, particularly the role of J chain and disulfide bonds, is essential for elucidating its function.

Purpose of the Study:

• To investigate the subunit structure and disulfide bonding patterns of polymeric immunoglobulin A (IgA).
• To determine the specific linkages involving the J chain in IgA polymers.

Main Methods:

• Analytical ultracentrifugation and polyacrylamide gel electrophoresis were used to analyze IgA structure.
• Reductive cleavage with mercaptoethylamine and dithiothreitol, followed by alkylation with [14C]-iodoacetamide, was employed.
• Chromatography on Bio-Gel P-200 in guanidine HCl was performed to assess subunit dissociation.

Main Results:

• Polymeric IgA was reduced to 10 S dimers and 7 S monomers, with dimers showing greater resistance to cleavage.
• Dimer and monomer IgA did not dissociate into H, L, or J chains under denaturing conditions, indicating intact interchain disulfide bonds.
• J chain was released only from the dimer upon reduction, and labeling studies indicated J chain is disulfide-bonded to two subunits in polymers.

Conclusions:

• The J chain in polymeric IgA is disulfide-bonded to only two subunits, with remaining subunits linked to each other.
• Polymeric IgA may not possess a covalently bonded circular structure, differing from immunoglobulin M (IgM).
• The precise structure of pentameric IgA could not be determined due to its low abundance.