What is Immunoglobulin D (IgD Antibody)?

• Immunoglobulin D (IgD) is a distinctive antibody type that plays a crucial role in the immune system. While its exact function is not yet fully understood, IgD is found in low concentrations in serum and is known to have unique characteristics. With a relative molecular mass of 185 kDa and a half-life of 2.8 days, IgD shares similarities with another immunoglobulin, IgE.
• Within the plasma membranes of immature B-lymphocytes, IgD accounts for approximately 1% of the total proteins present. It is commonly co-expressed with another cell surface antibody known as IgM. This co-expression occurs in a vast majority of B cells and enables them to exhibit both IgM and IgD, both of which are specific to the same antigen. This phenomenon is observed when B cells mature and transition from the bone marrow to populate peripheral lymphoid tissues.
• While IgD’s function remains somewhat enigmatic, its existence in a secreted form adds further complexity to its role. In blood serum, secreted IgD is present in minute quantities, constituting only 0.25% of the total immunoglobulins in serum. This secreted form of IgD is characterized by its monomeric structure, composed of two heavy chains belonging to the delta (δ) class, accompanied by two Ig light chains.
• Research and ongoing studies aim to unravel the precise functions and mechanisms behind IgD, shedding light on its significance within the immune system. Despite its relatively low concentration and mysterious nature, IgD plays an integral part in the complex network of antibodies that defend our bodies against pathogens and foreign substances.

Properties Of Igd

1. Abundance and half-life: IgD constitutes approximately 0.25% of the total serum immunoglobulins. It has a molecular weight (Mr) of 185,000 and a half-life of 2.8 days, similar to that of IgE.
2. Synthesis and turnover rate: The synthesis rate of IgD is at least 10 times lower than that of IgA, IgM, and IgG. Its turnover rate is 37% of the intravascular pool per day, higher than IgG, IgA, and IgM but lower than IgE.
3. Fragile structure: The IgD molecule has a long “hinge” region between the Fab and Fc fragments, making it susceptible to proteolytic degradation. This leads to the production of Fab and Fc fragments. The flexible nature of the molecule enhances its antigen binding ability.
4. Binding characteristics: IgD does not induce passive cutaneous anaphylaxis, and it does not bind to normal lymphocytes, neutrophils, or monocytes. It also does not cross the placenta. However, it binds nonspecifically to bacteria through the Fc fragment.
5. Antibody activity: IgD has antibody activity against specific antigens. Individuals with high levels of IgD can produce specific IgD antibodies in response to antigenic challenge. Specific IgD antibodies have been identified against various antigens, including cow’s milk, bovine serum albumin, diphtheria toxoid, insulin, wheat, tartrazine, and hepatitis B core antigen.
6. Surface expression: IgD was discovered on the surface of B cells and is the major antigen receptor isotype on most peripheral B cells. It is coexpressed with IgM. Plasma cells containing only IgD are rare, and IgD-containing plasma cells are more abundant in adenoids than in other lymphoid tissues.
7. Molecular characteristics: IgD heavy chains are covalently linked by one disulfide bridge, allowing greater freedom of the antigen-binding sites compared to other immunoglobulin isotypes. The δ chains from membrane-bound IgD have slightly slower electrophoretic mobility than serum monoclonal δ chains.
8. Signaling and association: IgD receptors on B lymphocytes transmit signals similar to IgM receptors but with different kinetics. The majority of cell-bound IgD is of the κ type, while most serum monoclonal IgDs are of the λ type. The association between δ heavy chains and λ light chains in IgD-secreting cells is preferential.
9. Function and role: The exact function of IgD is not fully understood. It is involved in B cell activation and regulation, enhancing antibody responses, participating in B cell memory, and potentially interfering with viral replication. IgD can induce the release of cytokines such as tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, IL-10, and leukemia inhibitory factor from peripheral blood mononuclear cells.
10. Evolutionary conservation: IgD is found in various mammalian and avian species, indicating its evolutionary advantage. While its role has been debated, studies using knockout mice suggest that IgD can largely substitute for IgM in B cell development and function.

Measurement Of Igd

The measurement of IgD, an immunoglobulin found in body fluids, has evolved over time with the development of more sensitive techniques. This article explores various methods used to measure IgD and discusses the challenges and considerations associated with each method. From traditional techniques like radial immunodiffusion (RID) to advanced methods such as radioimmunoassay (RIA) and enzyme immunoassay (EIA), this article provides an overview of the tools used in clinical laboratories to measure IgD levels.

• Radial Immunodiffusion (RID): RID is the most commonly used method in clinical laboratories for measuring IgD. Commercial reagents from reputable companies are readily available for this technique. However, RID has limitations, particularly in detecting low levels of IgD. Variability in the molecular size of antigens can affect the accuracy of measurements, as alterations in diffusion rates through the gel can lead to heterogeneous results. Moreover, the sensitivity of IgD to proteolysis can result in the overestimation of IgD concentration in old serum specimens measured by RID. To mitigate this issue, proteolysis inhibitors should be added to the serum before measurement.
• Nephelometry: Nephelometry, a technique used to measure the concentration of particles in a solution based on their light-scattering properties, has also been employed for IgD quantitation. Nephelometry offers improved sensitivity and precision compared to RID. Unlike RID, nephelometry is less affected by the molecular size of the protein being assayed. However, specific reagents for IgD are not readily available for nephelometry, limiting its widespread use for IgD measurement.
• Radioimmunoassay (RIA): RIA is a highly sensitive technique, approximately 1,000 times more sensitive than RID, and has been utilized for IgD measurement. RIA can detect IgD levels as low as 10 to 50 μg/liter, with further modifications pushing the sensitivity to 0.0008 U/ml. IgD stability during frozen storage has been observed in RIA, making it a reliable method for long-term sample preservation. RIA utilizing paper disks or two antibodies has demonstrated good precision with low coefficients of variation.
• Enzyme Immunoassay (EIA): EIA has also been employed for IgD measurement, offering an alternative to traditional methods like RID and RIA. Monoclonal anti-IgD antibodies are less effective than polyclonal antibodies in EIA, and the sensitivity of the test typically ranges from 4 to 10 μg/liter. EIA using microtiter plates and affinity-purified goat anti-human IgD has shown promising results with high linearity and low coefficients of variation.
• Standardization and Proficiency Testing: Accurate measurement of IgD relies on appropriate calibration and standardization. However, international reference preparations (IRP) for IgD are limited in availability. The World Health Organization standard, British Research Standard 67/37, is commonly used but lacks widespread reporting. Manufacturers must periodically verify and correct conversion factors to ensure accurate measurements. The College of American Pathologists offers proficiency testing for serum IgD, although participation in these surveys remains limited.

Structure of IgD Antibody

• The structure of Immunoglobulin D (IgD) antibody closely resembles that of other classes of immunoglobulins. It consists of heavy and light polypeptide chains, possesses a sedimentation coefficient of approximately 7S, and can be fragmented into Fab and Fc fragments.
• When IgD is secreted, it takes the form of a glycoprotein functioning as a monomeric antibody. It comprises two identical heavy chains belonging to the delta (δ) class, along with two identical Ig light chains. The structure of IgD includes two antigen binding areas, which consist of both light and heavy chains, offering a valency of 2. Notably, the heavy and light chains possess variable regions located at their N-terminal ends.
• On the surface of B cells, IgD exhibits additional amino acids at its C-terminal end, enabling it to anchor to the cell membrane. It also associates with the Ig-alpha and Ig-beta chains. The heavy and light chains are further divided into variable and constant regions. In addition to the disulfide bonds that link the chains together, intrachain disulfide links divide each chain into distinct areas referred to as domains.
• The light chains are comprised of two domains: one variable domain and one constant domain. On the other hand, the heavy chains consist of four domains: one variable domain and three constant-region domains. Notably, the IgD molecule features a long “hinge” region situated between the Fab and Fc fragments. This hinge region renders the molecule highly susceptible to proteolytic degradation, resulting in the production of Fab and Fc fragments. Moreover, it imparts flexibility to the molecule, thereby enhancing its ability to bind to antigens.
• Understanding the intricate structure of IgD antibody provides insights into its functional properties and contributes to unraveling its role within the immune system. The distinct characteristics of IgD enable it to participate in the complex network of immune responses, contributing to our body’s defense against pathogens and foreign invaders.

Functions of IgD Antibody

1. Antigen receptor on B cells: IgD serves as an antigen receptor on the surface of B cells. It plays a crucial role in recognizing and binding to specific antigens.
2. Regulation of B cell function: IgD is believed to be involved in regulating B cell function upon encountering antigens. It helps modulate the activation, proliferation, and differentiation of B cells.
3. Initiation of humoral immune response: When IgD, along with IgM, interacts with an antigen, it triggers internalization, processing, and presentation of the antigen to helper T cells. This interaction leads to B cell proliferation and differentiation into plasma cells, initiating the development of a humoral immune response.
4. Secreted IgD: IgD exists in a secreted form in blood, mucosal secretions, and on the surface of innate immune effector cells like basophils. Its specific function in these contexts is still not fully understood.
5. Activation of innate immune cells: IgD has the ability to bind to basophils and mast cells. This binding can activate these cells, stimulating them to produce antimicrobial factors. These factors contribute to respiratory immune defense in humans.
6. Potential role in allergic reactions: IgD has been proposed to have a role in allergic reactions, although the mechanisms are not completely understood. Further research is needed to elucidate its involvement in allergic responses.

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References

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