CD23 FcεR2 (Fc fragment of IgE, low affinity 2 receptor), BLAST-2, gp50-45, Low affinity IgE receptor
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 2 glycoprotein
B Cell
Monocyte
Hematopoietic Cell
Thymocyte
Epithelium
Dendritic Cell
Langerhans Cell
NK Cell
Platelet
Neutrophil
Eosinophil
Macrophage
T Cell
16 / 16
25 / 25
29 / 29
37 / 37
45 / 45

Expression
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.  


Structure
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.

MOLECULAR MASS
Cell Type Unreduced Reduced
B cells, monocytes 45 kDa 37kDa-16 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternate splicing yields 2 different isoforms differing by a 6 aa in the cytoplasmic region.

POST-TRANSLATIONAL MODIFICATION

CD23 proteolytic cleavage generates soluble CD23 fragments of various Mr.

Ligands
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
Molecule Comment
IgE
CD21
CD11b
CD11c




Function
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. 
 

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD23: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD23: No information.

ADDITIONAL INSIGHTS

The major critical question is the confirmation of the existence of other ligands than IgE in rodents.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2208P06734
MouseA43518P20693M99371
Antibodies
9P.25   View Reactivity
M-L233   View Reactivity

Revised June 25, 2008


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