IgD

**Structure and genetics** - Heavy chain: delta (δ). Light chains: kappa or lambda. - It is a monomer. The δ constant region gene (Cδ) lies immediately downstream of Cμ on chromosome 14. - Mature naive B cells co-express surface IgM and IgD with the same antigen specificity (same VDJ region). A long primary RNA transcript is alternatively spliced and polyadenylated to make either μ or δ heavy chains. No DNA recombination (class switching) is needed for this.

**Function** - Surface IgD on mature naive B cells (with IgM) acts as an antigen receptor. It signals through the Igα/Igβ (CD79a/CD79b) complex. - It marks B-cell maturation. Immature B cells express only IgM. IgD is added as the cell matures and leaves the bone marrow. - It may help set the activation threshold and support B-cell survival and tolerance (anergic B cells have low IgM but keep IgD). - Secreted IgD is a minor serum component, about 0.25% of serum Ig. It has a very short half-life and is prone to proteolysis (long hinge region). - Secreted IgD binds basophils and mast cells in the upper respiratory mucosa. It may promote antimicrobial and inflammatory responses and surveillance of respiratory pathogens. - It does not fix complement, cross the placenta, or act as an opsonin in a clinically meaningful way. Do not confuse it with IgG or IgE.

**Class switching** - Activated B cells switch isotype (IgM/IgD → IgG, IgA, or IgE). This depends on T-cell help via CD40–CD40L and cytokines. IgD is lost on switching. - Cytokine associations: IL-4 → IgG4/IgE. IL-5 and TGF-β → IgA. IFN-γ → IgG.

**Clinical significance** - IgD levels are not part of routine workup. - **Hyper-IgD syndrome (mevalonate kinase deficiency)**: - Autosomal recessive; mutation in *MVK*. - Presents with recurrent fever episodes in infancy, lasting days, with abdominal pain, lymphadenopathy, arthralgia, and rash. Attacks may be triggered by vaccination. - Serum IgD (and IgA) is elevated, but this is not pathogenic. Elevated urinary mevalonic acid is seen during attacks. - It is an autoinflammatory syndrome (IL-1 mediated), and anakinra (an IL-1 receptor antagonist) is used for treatment. - Distinguish it from Familial Mediterranean fever (*MEFV*, pyrin, colchicine-responsive, risk of amyloidosis, serositis). - **Multiple myeloma**: rare IgD myeloma subtype (about 1–2%) with a more aggressive course, frequent lambda light chains, and more renal involvement. The M-spike can be small or absent on SPEP because IgD is present at low levels, so immunofixation and free light chain assays help. - **B-cell neoplasms**: CLL cells typically co-express surface IgM/IgD (and CD5, CD19, CD20 dim, CD23).

**High-yield board pearls** - Surface IgM + IgD together = mature naive B cell (the two with the same antigen specificity). - IgD is not secreted in significant amounts and has no major established effector role (unlike IgG, IgA, IgE, and IgM). - Co-expression is by alternative RNA splicing, not by class switching. - Hyper-IgD syndrome: periodic fever + mevalonate kinase deficiency.