Antibody Isotypes: IgD

Immunoglobulin D constitutes approximately 0.25% of all serum immunoglobulins in the body, and there is still debate over the specific role for IgD. There is evidence suggesting they may play a part in basophil and mast cell activation to produce antimicrobial factors, as well as determining if antigens will activate B cells.¹

In humans, although most mature B cells express both surface IgD and IgM by alternative splicing of preRNA, a small group of mucosal B cells from the nasopharyngeal lymphoid tissue expresses solely IgD. This secreted IgD can be found in circulation, nasopharyngeal, oral and lachrymal secretions, in addition to being on the surface of myeloid innate effector cells, such as basophils, mast cells and monocytes. When IgD is basophil-bound and cross-linked by an antigen, the release of cytokine IL-4 will trigger an increase in IgG production, thus enhancing humoral immunity by the mucosal immune surveillance.²

Moreover, the IgD molecule has a lengthy hinge region between Fab and Fc, which is the likely cause for IgD to be susceptible to proteolysis, although this increases flexibility and thus improves antigen binding. Interestingly, the hinge region also appears to regulate the responsiveness of B cells, as Übelhart et al. (2015) discovered when deleting it resulted in IgD being reactive to monovalent antigens, while transferring the hinge to IgM resulted in responsiveness only to polyvalent antigens.³ 

Meanwhile, serum IgD is thought to represent an early marker of B-cell activation. Other potential functions of IgD include having a regulatory role, the generation and maintenance of B-cell memory, and as an inducer of TNF-α, IL-1β, and IL-1 receptor antagonist. Furthermore, serum IgD measurement can be important for monitoring of IgD myelomas by measuring the protein concentration of the M spike in serum protein electrophoresis.²

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References: 

1. Vladutiu, A. O. (2000). Immunoglobulin D: Properties, Measurement, and Clinical Relevance. Clinical and Diagnostic Laboratory Immunology, 7(2), 131. https://doi.org/10.1128/CDLI.7.2.131-140.2000

2. Gutzeit, C., Chen, K., & Cerutti, A. (2018). The enigmatic function of IgD: some answers at last. European Journal of Immunology, 48(7), 1101–1113. https://doi.org/10.1002/EJI.201646547

3. Übelhart, R., Hug, E., Bach, M. P., Wossning, T., Dühren-Von Minden, M., Horn, A. H. C., Tsiantoulas, D., Kometani, K., Kurosaki, T., Binder, C. J., Sticht, H., Nitschke, L., Reth, M., & Jumaa, H. (2015). Responsiveness of B cells is regulated by the hinge region of IgD. Nature Immunology 2015 16:5, 16(5), 534–543. https://doi.org/10.1038/ni.3141