IgD is primarily of interest in its membrane form, as the soluble form of IgD is found in relatively modest concentrations in the blood and other body fluids.
present on all mature, naïve B cells
The cell surface form of IgD is found along with IgM on all mature, naïve B cells, where it appears capable of transducing activating and tolerizing signals. Simultaneous cell surface expression of two heavy chain isotypes expressing the same VH domains and the same light chains occurs via differential RNA splicing. IgD appears optimized for responding to multivalent antigen in immune complexes as opposed to responding to monovalent antigen. This reflects, in part, differences in charge and O-linked glycosylation between the IgM and IgD hinge regions. Higher IgD expression by anergic B cells helps keep them quiescent against monovalent autoantigens, reducing the risk of autoreactive responses. Absence of IgD leads to the retardation of T-dependent immune responses, antibody production, and affinity maturation.
IgD appears optimized for responding to multivalent antigen
B cell receptors reside as nanoclusters, or protein islands, on the surface of the cell. Just like IgM, the membrane form of IgD associates noncovalently with Ig-α (CD79a - CD79b|CD79a) and Ig-β (CD79b). However, on the B cell surface these two isotypes are functionally segregated and they can be stimulated independently from each other. In resting B cells, IgD-BCRs colocalize with CD19 and CXCR4, whereas IgM-BCRs gain proximity with CD19 only upon activation. IgD is required for CXCR4 signaling in mature B cells and thus influences the migration of mature B cells into secondary lymphoid tissues and induces actin cytoskeleton remodeling upon antigen binding.
In the serum, IgD exhibits greater sensitivity to proteolytic cleavage than IgM, which is consistent with a relatively short serum half-life of only 2.8 days.
The relatively long hinge region is a primary target for proteolysis.
The shorter half-life, 2.8d
the relatively long hinge region corresponds to appear optimized for responding to multivalent antigen
The microbiota can help drive class switch recombination from IgM to IgD.
IgD-producing B cells in the upper respiratory mucosa can participate in host defense against pathogens relevant to this anatomical environment. Secreted IgD antibodies can bind to basophils and mast cells.
IgD bound to basophils via galectin-9 and CD44 can amplify humoral Th2 responses. When these antibodies are cross-linked by cognate antigen, the basophils release potent mediators that influence immune reactivity, inflammation, and pathogen viability. Moreover, IgD activated mast cells can induce IgE synthesis in nasal polyps.