Polymerization of IgM

Immunoglobulins play a vital role in our immune system, where their main job is to identify and neutralize foreign substances such as bacteria and viruses. Immunoglobulin M (IgM), one of the five types of antibodies, stands out due to its unique capability of polymerization. IgM is produced by B lymphocytes and is the earliest type of antibody that is expressed on the cell surface in response to antigens. Every IgM antibody molecule is made up of five or six single units, or monomers, that are interconnected via disulfide bonds along with a J-chain peptide. These linkages form larger molecules that are either pentamers or hexamers. The ability to polymerize in such a manner is unique to IgM, and it grants it a high valency. This means that it can bind to multiple mannose residues on pathogens at once, enhancing its effectiveness in neutralizing threats to our bodies. This article aims to explicate the process through which this polymerization takes place.

Polymerization of IgM
The polymerization process of IgM commences in the endoplasmic reticulum (ER) of B cells. Each IgM monomer is made up of two heavy chains and two light chains linked by disulfide bonds. The heavy chains contain an extra domain, named Mu, which is significant for the polymerization process. Cysteine residues in the C-terminal of the Mu domain play a critical role in the polymerization. These residues can form disulfide bonds with residues in other monomeric units, leading to the formation of pentamers or hexamers. Experimental evidence shows that the cysteine residues C414, C575, and C414 in the invariant region play a critical part in this process. After the initial formation of the pentameric or hexameric structure, an additional peptide chain, the J-chain, is incorporated. The J-chain facilitates the formation of disulfide bonds between adjacent monomers, thereby stabilizing the entire polymer. Furthermore, the J-chain also has a critical role in IgM secretion from B cells, helping transport IgM to the cell surface and aiding with the binding to the poly Ig receptor, which enables subsequent transcytosis across epithelial cells.