|CD23||FcεR2 (Fc fragment of IgE, low affinity 2 receptor), BLAST-2, gp50-45, Low affinity IgE receptor|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Lineage Restricted Molecule|
Type 2 glycoprotein
|16 / 16|
25 / 25
29 / 29
37 / 37
45 / 45
|CD23 is expressed on human cells is on B cells, monocytes, and the FDC apical light zone such as T cells, platelets, eosinophils, neutrophils, Langerhans cells and more weakly on a variety of other hematopoietic cells including T cells, follicular dendritic cells, eosinophils, NK cells, Langerhans cells thymic epithelium and platelets. On B cells, CD23 expression is restricted to mIgM+mIgD+ cells and is lost upon differentiation into plasma cells. CD23 on B cells is upregulated following B cell activation, CD40 ligation, or in response to IL-4 or IL-13. In rodent B cells is expressed on FDC. |
|MOLECULAR FAMILY NAME: Belongs to the C type lectin family.|
CD23 is a single-pass type-2 homotrimeric glycoprotein. It contains an extracellular domain which contains a C-type lectin domain with 3 21 aa repeats which form an a-helical coiled-coil stalk that results in trimer formation., a transmembrane and a cytoplasmic domain. There are 2 alternatively spliced forms called FceRIIα and FceRIIb, differing by 6 aaat the N-terminal cytoplasmic region and are expressed on different cell types. FcεRIIα is restricted to resting B cells, whereas FceRIIb is expressed by other cell types and is induced upon B cell activation. Proteolytic cleavage of the membrane-bound form generates a soluble product of 45 kDa, which can be further degraded into 37 kDa, 29 kDa, 25 kDa and 16 kDa fragments that retain their lectin head groups.
Alternate splicing yields 2 different isoforms differing by a 6 aa in the cytoplasmic region.
CD23 proteolytic cleavage generates soluble CD23 fragments of various Mr.
|The Fc region of IgE, CD21, and the integrin a chains CD11b and CD11c are ligands for CD23. In each case the C-type lectin domain of CD23 is responsible for ligand binding. Low affinity of IgE binding to CD23 is a protein-protein interaction that involves the 3rd constant domain of the IgE heavy chain. CD23 interacts with 2 sites on CD21 with 1 site, CCP domains 5-8, is a lectin-carbohydrate type of interaction whereas the other, CCP domains 1-2, is a protein-protein interaction. CD23 binds to the integrins CD11b/CD18 and CD11c/CD18, but not CD11a/CD18. This interaction is at least partly dependent on lectin-carbohydrate binding. CD23 has been shown to associate non-covalently with MHC class II in B cells, by co-immunoprecipitation analyses in weak detergent.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD23
|CD23 is a low affinity IgE receptor and is involved in the regulation of IgE synthesis. Following binding of IgE and IgE-containing immune complexes, CD23 exerts a negative feedback signal the reduces IgE synthesis. Consistent with this function, mice rendered deficient for CD23 have 1 major phenotype, namely high serum IgE levels and increased specific IgE responses to T cell dependent antigens. Transgenic mice that overexpress CD23 show impaired IgE-mediated antigen presentation. The in vivo role of soluble CD23 (sCD23) is not clear, but it is proposed that sCD23 can function as a cytokine that enhances IgE synthesis, probably through binding to surface membrane IgE and CD21. The role of CD23 as a cell-cell adhesion molecule is also not clear but the CD23 interaction with CD21 may be important in enhancing IgE synthesis, in B cell homotypic adhesion and in the rescue of germinal center B cells from apoptosis. The ligand pairing of CD23 with the integrins CD11b/CD18 and CD11c/CD18 is thought to play a role in monocyte activation. CD23 functions in the regulation of IgE synthesis and in the pro-inflammatory function, and in the triggering of monokine release by human monocytes such as TNF, IL-1, IL-6, and GM-CSF. The 2 forms of CD23 have been implicated in different signaling pathways and specific functions. The Tyr 6 aa of FceRIIa is involved in endocytosis and the Asp-Pro motif 2-3 aa of FCeRIIb is associated with phagocytosis. Knockout miced have elevated levels of IgE and impaired IgE-mediated antigen presentation. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD23 IN INTACT ANIMAL
CD23 is an A allergy. A1 negative feedback regulation of IgE synthesis of CD23-/- mice have elevated serum IgE levels compared to WT mice. Some anti-CD23 antibodies decrease human IgE production. A2 IgE-mediated Ag presentation is impaired in CD23-/- mice. B inflammation anti-CD23 mAb treatment decreased the severity of collagen-induced arthritis. C chronic lymphocyte leukemia (CLL) serum soluble CD23 level is a significant prognostic marker in CLL that discriminates, at the early stage of the disease and patients at high risk of disease progression. CD23 is a useful marker in differentiation of small lymphocytic and mantle cell lymphomas.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD23: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD23: No information.
The major critical question is the confirmation of the existence of other ligands than IgE in rodents.
Database accession numbers
Revised June 25, 2008