IgD: the lesser known antibody 

Shan et al., 2018. Graphical Abstract

Shan et al., 2018. Graphical Abstract

Unlike immunoglobulin (Ig) M, IgG, IgA and IgE, the role of IgD in antibody mediated immunity is unknown. IgD is co-expressed with IgM on mature B cells, and is best known for its function as a B cell antigen receptor. Upon antigen exposure and B cell interaction with T follicular helper T cells, B cells down regulate IgD and differentiate into IgM secreting plasma cells. Some of these plasma cells can secrete IgD, which make up approximately 1% of total antibodies. Unlike IgM, IgD does not recruit pro-inflammatory complement proteins, suggesting that it may play a role in non-inflammatory mediated immunity. The specific contribution of secreted IgD has not been explicitly defined.

Shan et al., researchers from Spain, Sweden, Switzerland and USA, showed that secreted IgD can bind to basophils via galectin-9 and CD44, resulting in increased basophil expression of IL-4. Using in-vivo subcutaneous immunisation murine models Shan et al., showed that IgD via basophils contributes but is not necessary for induction Th2 cell mediated immune responses. The study also also demonstrated that IgD antibodies can react to food derived proteins such as lactoglobulin, a milk derived protein. Finally, to determine the relationship between IgD and IgE (antibody that also bind to galectin-9) Shan et al., used an acute lung inflammation model to show that IgD inhibits IgE-induce basophil degranulation, a finding they also confirmed in  humans.

In summary Shan et al., illustrated one of the functional roles of IgD where, secreted IgD binds to basophils via the CD44 interaction protein galectin-9. Binding then induces expression of IL-4, Il-5 and IL-13 by basophil-bound IgD, creating an immune microenvironment favouring Th2 cell type activity. Finally, IgD also dampens IgE mediated immunity, could be used  to attenuate IgE dependent allergic reactions to food allergins.

Journal Article: Shan et al., 2018. Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44. Immunity


Article by Cheleka AM Mpande

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation