CD22 BL-CAM, Lyb-8, Siglec-2, Bgp135, LPAP
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
B Cell
130 / 130
140 / 140

Expression
CD22 is expressed on the surface of mature B cells and corresponding malignancies.  Early B cells have cytoplasmic CD22.  In mice, expression appears on the cell surface simultaneously with surface IgD, and is found on most mature B cells, where expression is closely correlated with surface IgD.  Expression is lost with terminal differentiation on B cells and is absent on plasma cells.  Activation of B cells via surface Ig increases CD22 expression.


Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.

CD22 is a single-pass type-1 glycoprotein.  It contains an extracellular domain which contains 6 Ig-like C2-type domains and 1 Ig-like V-type domain both of which are N- and O-glycosylated , a transmembrane domain and an 140 aa cytoplasmic domain containing 4 ITIM motifs and a sialic acid binding region is located in domqin 1 however the presence of domain 2 is essential for ligand binding.  It is a member of a structurally related group of IgSF domain-containing sialic acid binding proteins called the sialoadhesin family, which includes sialoadhesin (CD33) and myelin-associated glycoprotein (MAG).  The 140 kDa molecule is the major form found on the B-cell surface but low level expression of a 130 kDa isoform, lacking the fourth Ig-like domain, is also detected on most B cells.  CD22 antibodies may recognize carbohydrate determinants on the CD22 molecule because all three so far epitopes are destroyed by treatment are destroyed by treatment with endoglycosidase F. 

MOLECULAR MASS
Cell Type Unreduced Reduced
Unspecified 140 kDa 130 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  CD22 has a variable splicing of exons 6, or 6 and 7 which yield different isoforms.  An isoform lacking the 4th Ig-like is expressed on the membrane of most B cell lines.

POST-TRANSLATIONAL MODIFICATION

CD22 is N-glycosylated, O-glycosylated, and phosphorylated after activation through BCR or CD22 itself.

Ligands
The CD22 binds to sialoglycoconjugate NeuAc a2 ->6Gal b1 ->4GlcNAc which is widely present on N-linked carbohydrates.  The binding site lies on the GFCC'C'' b sheet of the membrane-distal IgSF domain and includes a 101 residue arginine conserved in all sialoadhesin family proteins.  CD22 forms a loose complex with the B cell antigen receptor (BCR).  The cytoplasmic domain is tyrosine phosphorylated upon ligation of the BCR and associates, via SH2 domains, with the tyrosine phosphatase SHP-1, the tyrosine kinase Syk, and phospholipase C-g1.  The tyrosine kinase Lck and phosphatidylinositol 3-kinase have also been reported to bind to the cytoplasmic domain.

LIGANDS AND MOLECULES ASSOCIATED WITH CD22
Molecule Comment
p72sky Tyrosine kinases
p53/56lyn Tyrosine kinases
Phosphatidylinositol-3 kinase Tyrosine kinases
SHP1 Tyrosine phosphatase
Phospholipase Cg1
 
Expression of 2-6 sialic acids occurs on B cells, T cells, monocytes, neutrophils and erythrocytes.  CD45, IgM and haptoglobin have been proposed as putative natural ligands.  A small percentage of surface immunoglobulins are associated with CD22. 
 

Function
CD22 functions as an adhesion and signaling molecule and may act in cell-cell interactions. CD22 binds sialylated ligands of erythrocytes, all leukocytes and endothelial cells.  CD22 binds numerous glycoproteins, including all isoforms of CD45, IgM, and haptoglobulin however, physiologically active ligands have not been identified.  The ligand binding of CD22 influences its intracellular signaling domain and is needed for inhibition of the B cell receptor signal.  Cross-linking of CD22 and BCR leads to rapid tyrosine phosphorylation, enabling binding of several kinases and phosphorylation, involved in siganl effector functions , including tyrosine phosphqtqse SHP1, p72sky, p53/56lyn, PI-3K and phospholipase Cg (PLCg).  Targeted disruption of CD22 in mice results in a reduced level of surface IgM on peripheral B cells, enhanced Ca++ flux in response to Ig signaling and variable proliferative responses to surface Ig crosslinking.  Several studies have shown there is a reduced response to thymus independent antigens.  CD22 down-modulates the B cell activation threshold, presumably through its association with SHP-1 and other signaling molecules.  The CD22-knockout data support a role for CD22 in limiting antigen receptor signaling although a positive role in certain B cell response cannot be excluded.  Mice deficient in CD22 show exaggerated antibody responses to antigen and have raised levels of autoantibodies.  CD22 can also mediate cell adhesion through its interaction with cell surface molecules bearing the appropriate sialoglycoconjugates, but only when the cells expressing CD22 do not themselves carry these sialoglycoconjugates.  Although the significance of sialic acid binding by CD22 is not known, ligation-induced restribution of CD22 on B cells decreases the BCR activation threshold, providing a plausible link between the adhesion and signaling.  CD22-knockout mice have relatively normal B cell development and the response to thymus independent antigens is relatively intact but fewer mature B cells with less surface Ig and are more sensitive to triggering through the B cell receptor.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD22 IN INTACT ANIMAL

CD22 has been used as a target in antibody treatment of leukemia and lymphoma.  CD22 is useful for diagnosis and experimental therapy of mature B cell malignancies.  

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD22: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD22: No information.

ADDITIONAL INSIGHTS

The major critical question still is the in vivo function of CD22 and the identification of a bona fide natural ligand or ligands.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 933P20273
Mouse-CD22A46512P35329L02844,L16928
Antibodies
HIB22   View Reactivity
Mc64-12   View Reactivity
RFB-4   View Reactivity
To15   View Reactivity

Revised June 25, 2008


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