Immunoglobulin D (IgD) is one of the five primary classes of antibodies, or immunoglobulins, found in the human body. Discovered in 1965, its specific functions remained largely uncertain for many years. IgD is present in blood serum at significantly lower concentrations compared to other antibodies like Immunoglobulin G (IgG) and Immunoglobulin M (IgM), representing approximately 0.25% of total serum immunoglobulins. This low serum presence historically made its biological role challenging to understand.
Structure and Location of Immunoglobulin D
IgD exhibits a monomeric structure, composed of two identical heavy protein chains and two identical light protein chains. These chains are held together by disulfide bonds, and IgD has a molecular weight of approximately 185 kDa. A distinctive feature of IgD is its relatively long hinge region, which provides flexibility to the molecule.
Most IgD is not freely circulating but is anchored to the surface of B cells, a type of white blood cell. Here, it functions as a B cell receptor (BCR), alongside IgM, enabling the B cell to recognize specific foreign substances. This surface-bound location on B cells distinguishes IgD from other antibody classes primarily found in soluble form in serum.
The Function of Immunoglobulin D
One primary role of IgD is its function as an antigen receptor on the surface of mature B cells. When an antigen binds to surface-bound IgD, it helps initiate B cell activation and differentiation. This binding signals the B cell to proliferate and differentiate into antibody-producing plasma cells. The flexibility of membrane-bound IgD, due to its long hinge region, may allow it to bind to antigens with widely spaced epitopes more effectively than the more rigid IgM molecule.
Beyond its role as a B cell receptor, secreted IgD is involved in mucosal immunity, particularly in the upper respiratory tract. This secreted IgD can bind to immune cells such as basophils and mast cells. Upon binding, IgD activates these cells to release antimicrobial substances like cathelicidin, and pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-4 (IL-4), and interleukin-13 (IL-13). These mediators contribute to defense against respiratory pathogens and can also stimulate B cells.
Immunoglobulin D Levels and Associated Conditions
Variations in IgD levels can sometimes point to underlying health conditions, though isolated IgD levels are not always indicative of disease. A selective deficiency of IgD is relatively common and often presents without symptoms. Individuals with very low or undetectable serum IgD levels typically do not experience an increased risk of infections or other health issues, especially if other immunoglobulin levels are normal. This suggests that while IgD has roles, its absence alone does not severely compromise overall immune function.
Elevated IgD levels are a hallmark of Hyper-IgD syndrome (HIDS), a rare genetic autoinflammatory disorder. This condition is characterized by recurrent episodes of fever, often accompanied by symptoms such as abdominal pain, joint pain, swollen lymph nodes, and skin rashes. HIDS is caused by mutations in the mevalonate kinase (MVK) gene, leading to a partial deficiency of the mevalonate kinase enzyme and impaired control of inflammatory mediators.
IgD can also be overproduced in a rare and aggressive form of multiple myeloma, a cancer affecting plasma cells. This specific subtype, IgD myeloma, accounts for less than 2% of all multiple myeloma cases. Patients often present with advanced disease and may experience complications such as kidney failure, high calcium levels, and extensive bone lesions. The low secretion levels of IgD can make its detection challenging through standard protein electrophoresis tests.