FcεRII (CD23) is the low-affinity receptor for IgE, and it is thought to play an important role in regulating IgE production. CD23 is a type II membrane protein with a C-type lectin domain that trimerizes on the cell surface, and this trimer binds to IgE-Fc through the lectin homology region in a calcium-dependent reaction. Transgenic mice overexpressing CD23 have low levels of serum IgE, suggesting that IgE production is inhibited by high CD23 levels. CD23 exists in two isoforms, CD23a and CD23b.
Function of CD23
- Role of CD23 and Soluble CD23 (sCD23) in IgE Regulation
- CD23 and Soluble CD23 Are Multifunctional Molecules
The initial studies have indicated that IgE binding molecules (IgE-BF) released by CD23-bearing B cells are capable of increasing the spontaneous in vitro IgE synthesis by in vivo preactivated B cells present in the blood of allergic donors. These IgE-BF were subsequently found to be identical to sCD23. The observations that intact or F(ab')2 fragments of anti-CD23 mAbs are capable of suppressing IgE have been documented by several laboratories. Therefore, membrane CD23 and its soluble fragments play a role in the regulation of IgE synthesis: CD23 may inhibit IgE production at a stage before B-cell switching, whereas soluble CD23 may enhance IgE production by IgE-committed B-cells.
Fig.1 Regulation of IgE by CD23. (Corry, 1999)
Membrane-bound CD23 may exert different functions according to the cell types on which it is expressed. Low affinity IgE receptor or CD23 mediates IgE-dependent cellular cytotoxicity against parasites as well as IgE-dependent release of inflammatory mediators. More recently, it has been proposed that CD23 plays a major role in IgE-dependent antigen presentation. Soluble CD23 fragments, besides their IgE regulatory activities, exert several effects, either alone or in synergy with IL1 on a large variety of hematopoietic cells.
Soluble CD23 as Disease Biomarkers
sCD23 levels appear to be upregulated in a plethora of diseases. Elevated sCD23 levels have been found in association with allergic diseases, including asthma and atopic dermatitis. Chronic lymphocytic leukemia (CLL) is currently the only disease in which sCD23 is used as a clinical biomarker. CLL patients show significantly higher levels of serum sCD23 when compared to healthy controls. In AIDS patients, sCD23 appears to be a predictive biomarker for the development of non-Hodgkin lymphoma. Recently, elevated serum levels of sCD23 were described in patients with pancreatic cancer. Several reports describe elevated sCD23 levels in serum and synovial fluid of patients with rheumatoid arthritis. Investigations in allergic rats revealed that enhanced intestinal transepithelial antigen transport is mediated by IgE and FcεRII. Blocking the binding of IgE to its receptor inhibits the transepithelial antigen transport and the hypersensitivity reaction, and might be a model for treatment strategies for allergic food reactions.
The structure-function relationships of the CD23 protein are increasingly well understood and demonstrate that there is considerable functional flexibility in the protein, regulated by specific interaction surfaces, single key residues, or the oligomeric state of the protein. The validity of CD23 as a target for therapeutic intervention is clear. The use of small peptide-based agents, such as p30A, is likely to guide the development of peptidomimetic and other small organic compounds that aim to antagonize the interactions of CD23 with specific ligands to therapeutic benefit.
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Reference
- Corry, D.B.; Kheradmand, F. Induction and regulation of the IgE response. Nature. 1999, Nov 25:B18-23.
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