Immunoglobulin M (IgM)- Structure and Functions

Immunoglobulins, also known as antibodies, are glycoproteins produced by plasma cells in response to foreign antigens. They are essential for the adaptive immune system to recognize and eliminate pathogens and other harmful substances. Immunoglobulins can be classified into five major classes: IgA, IgD, IgE, IgG, and IgM. Each class has a distinct structure and function in the immune system.

Immunoglobulin M (IgM) is the largest and most primitive of the immunoglobulin classes. It is the first antibody to be produced during an immune response and plays a crucial role in initiating and mediating the primary immune response. IgM can exist in two forms: a pentamer that circulates in the blood and a monomer that is expressed on the surface of B cells. Both forms have unique features and functions that contribute to the immune defense.

In this article, we will explore the structure and functions of IgM in detail and discuss its significance in health and disease. We will also compare IgM with other immunoglobulin classes and highlight its advantages and disadvantages in the immune system. By the end of this article, you will have a better understanding of the role of IgM in immunity and its implications for diagnosis and treatment of various diseases.

Immunoglobulin M (IgM) is a type of antibody that can exist in two forms: a pentamer and a monomer. The pentamer form is the most common one in the blood, while the monomer form is found on the surface of B cells.

Pentamer and monomer forms

The pentamer form of IgM consists of five identical four-chain units, each composed of two heavy chains (μ) and two light chains (κ or λ). The heavy chains have one variable domain (VH) and four constant domains (CH1-CH4), while the light chains have one variable domain (VL) and one constant domain (CL). The pentamer is held together by disulfide bonds between the CH4 domains of the heavy chains. The pentamer also has a J-chain, a small polypeptide that links the CH4 domains and initiates the polymerization of IgM subunits.

The monomer form of IgM is similar to the four-chain unit of the pentamer, except that it has an extra hydrophobic domain at the C-terminus of each heavy chain. This domain anchors the monomer to the plasma membrane of B cells, where it serves as a B cell receptor (BCR) for antigen recognition and activation.

B cell surface expression

IgM is one of the first antibodies to be expressed on the surface of B cells during their development. It is co-expressed with IgD, another type of antibody that has a similar structure but a different heavy chain class (δ). Together, IgM and IgD form the BCR complex, which also includes several accessory proteins that transduce signals from antigen binding. The BCR complex enables B cells to respond to antigens and differentiate into plasma cells or memory cells.

Composition in blood

IgM is the third most abundant immunoglobulin in human serum, after IgG and IgA. It accounts for about 5-10% of the total immunoglobulin pool. The average concentration of IgM in serum is about 1.5 mg/mL, but it can vary depending on age, health status, and exposure to antigens. IgM has a relatively short half-life of about 5 days in circulation.

J-chain association

The J-chain is a small polypeptide that is synthesized by plasma cells along with IgM subunits. It has two cysteine residues that form disulfide bonds with the CH4 domains of two adjacent IgM subunits, linking them together into a pentamer. The J-chain also has a binding site for the polyimmunoglobulin receptor (pIgR), which mediates the transport of IgM across epithelial cells to mucosal surfaces. The J-chain is essential for the formation and secretion of pentameric IgM, as well as for its function in complement activation and agglutination reactions.

IgM is the first antibody produced and the prime mediator of the primary immune response. It is also the first type of immunoglobulin produced by newborns and plays a role in the development of some autoimmune diseases. Its efficiency in combining with antigen is of particular importance until sufficient quantities of IgG antibody have been synthesized in the body.

Some of the functions and significance of IgM are:

• It binds to antigens and activates the complement system, which helps to destroy pathogens and prevent their invasion of blood.
• It is responsible for agglutination, neutralizing, and cytolytic reactions and is of vital importance in complement activation and agglutination reactions to combat pathogens.
• It interacts with several other physiological molecules such as:
  • Binding with complement component C1 and activating the classical pathway.
  • Binding to the polyimmunoglobulin receptor (pIgR) in a process that brings IgM to mucosal surfaces, such as the gut lumen and into breast milk. This has a role in mucosal defense.
  • Binding to Fc receptors on phagocytic cells and enhancing their activity.
• It has high avidity for antigens due to its polyvalency and is very efficient per molecule in dealing with pathogens especially early in the immune response. It can bind antigens present at low levels, and non-protein antigens, such as carbohydrates or lipids present on microbial surfaces.
• Elevated levels of IgM can be a sign of recent infection or exposure to antigen.

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