Background
IgD is an immunoglobulin found in 1965 and is one of the immunoglobulins that can be found in the low serum levels. It has two versions: mIgD and sIgD. IgD accumulates only on the surface of B lymphocytes, and in tiny amounts in serum. The secreted IgD primarily serves to identify soluble antigens and induce protective humoral responses, while the membrane-bound version is a marker for B cell growth, differentiation and maturation. In addition to peripheral blood, sIgD can be detected in various bodily fluids such as nasal cavity fluid, tears, and saliva. Most IgM-IgD+ B cells in the upper airways secrete sIgD that attracts foreign bacteria and viruses, improving mucosal protection. In addition, sIgD also binds to basophils in human peripheral blood and tonsils, which release inflammatory cytokines (IL-4, IL-13, BAFF, TNF) and antimicrobial peptides, and therefore basophil involvement in the immune system. Before B cells mature, they express only IgM; however, IgD expression begins when B cells exit the bone marrow and enter secondary lymphoid organs. The presence of mIgD on B cell surfaces acts as a B cell receptor (BCR), promoting normal B cell differentiation, antigen-dependent activation, and the induction of self-tolerance.
Figure 1. IgD in the aerodigestive mucosa
(Source: Chen K, et al. 2020)
IgD is a tetrameric protein - it contains two heavy chains and two light chains that bond disulfide chains together into a single molecule. It is roughly 185 kDa in molecular weight and it has a hinge area that is quite long and is prone to proteolytic degradation, hence its half-life is short. IgD is longer than IgM and this may make it more malleable. Second, IgD's architecture is highly variable from one species to another: in fish, for instance, IgD doesn't have a hinge region, while in mammals IgD does.
We don't yet know exactly how IgD functions in the immune system, but it's been shown to play a role in various immune systems. The first is that IgD acts as a surface receptor on B cells and it plays a role in antigen detection and signalling. Its signaling mechanism is similar to that of IgM, but with different kinetics. Secondly, IgD also plays a significant role in regulating humoral immune responses; in certain cases, it can substitute for the functions of IgM or IgG. Additionally, IgD is involved in the activation and differentiation processes of lymphocytes, contributing to responses during upper respiratory infections and inflammatory reactions. Due to its unique position in the immune system, IgD could be used to prevent and treat disease. Researchers in rheumatoid arthritis, for example, found that changes in IgD are linked to disease severity, and that anti-IgD antibodies can kill mature B cells, thereby alleviating symptoms. Moreover, IgD's antibody response in some infectious diseases (rubella, tuberculosis) suggests that it is potentially diagnostic and therapeutically useful.
Alternative Names
Native Human immunoglobulin D Myeloma Plasma
References
- 1. Gutzeit C, et al. The enigmatic function of IgD: some answers at last. Eur J Immunol. 2018 Jul;48(7):1101-1113.
- 2. Chen K, et al. Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA. Nat Rev Immunol. 2020 Jul;20(7):427-441.