• BL-CAM
• Lyb8

MAJOR LINKS FOR CD22  

• NCBI LocusLink Record: 933
• Mendelian Inheritance in Man (OMIM): 107266
• SwissProt annotated protein record: P20273

CELLULAR FUNCTION OF CD22  

• Adhesion molecules
• Signaling molecule
• 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, variable proliferative responses to surface Ig crosslinking. Several studies observed a reduced response to thymus independent antigens **
• 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**

DISEASE RELEVANCE OF CD22 AND FUNCTION OF CD22 IN INTACT ANIMAL Link to additional info in FORUM  

• Antibody treatment of leukemia and lymphoma
• CD22-knockout mice have relatively normal B cell development and the response to thymus independent antigens were relatively intact**

• Families in which CD22 is a member
  • CD22-->SiGLec-->sialoadhesin-->immunoglobulin supergene family
  • CD22-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD22  

• Single chain type I transmembrane molecule which contains seven Ig-like domains
• Intracytoplasmic tail contains six tyrosines, four of which are found in two homologous regions containing "ITIM" motif

MOLECULAR MASS OF CD22  

POST-TRANSCRIPTIONAL MODIFICATION OF CD22  

• Variable splicing of exons 6, and 6 and 7 yield different isoforms
• An isoform lacking the 4th Ig-like is expressed on the membrane of most B cell lines

POST-TRANSLATIONAL MODIFICATION OF CD22  

• N-glycosylated
• O- glycosylated
• Phosphorylated after activation through BCR or CD22 itself

SUBSTRATES FOR CD22   - No information

ENZYMES WHICH MODIFY CD22   - No information

LIGANDS FOR CD22 AND MOLECULES ASSOCIATED WITH CD22  

• a2-6 sialic acids expressed on B cells, T cells, monocytes, neutrophils and erythrocytes
• CD45, IgM and haptoglobin have been proposed as putative natural ligand
• Small percentage of surface immunoglobulins associated with CD22
• ---WARNING---REVIEWER/EDITOR QUESTION OUTSTANDING IN THIS SECTION---

• B cell specific expression
• Surface expression on mature B cells
• Cytoplasmic expression on late pro- and early pre-B cells

• Major critical question still is the in vivo function of CD22 and the identification of a bona fide natural ligand or ligands

SELECTION OF OTHER CD22-SPECIFIC REFERENCE MAB  

REVIEWS

PRIMARY CITATIONS

1. Campbell MA,Klinman NR Phosphotyrosine-dependent association between CD22 and protein tyrosine phosphatase 1C. Eur J Immunol 1995 25:1573 PubMed

2. Doody GM,Justement LB,Delibrias CC,Matthews RJ,Lin J,Thomas ML,Fearon DT A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 1995 269:242 PubMed

3. Dorken B,Moldenhauer G,Pezzutto A,Schwartz R,Feller A,Kiesel S,Nadler LM HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes. J Immunol 1986 136:4470 PubMed

4. Engel P,Nojima Y,Rothstein D,Zhou LJ,Wilson GL,Kehrl JH,Tedder TF The same epitope on CD22 of B lymphocytes mediates the adhesion of erythrocytes, T and B lymphocytes, neutrophils, and monocytes. J Immunol 1993 150:4719 PubMed

5. Engel P,Wagner N,Miller AS,Tedder TF Identification of the ligand-binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand. J Exp Med 1995 181:1581 PubMed

6. Law CL,Torres RM,Sundberg HA,Parkhouse RM,Brannan CI,Copeland NG,Jenkins NA,Clark EA Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles. J Immunol 1993 151:175 PubMed

7. Leprince C,Draves KE,Geahlen RL,Ledbetter JA,Clark EA CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proc Natl Acad Sci U S A 1993 90:3236 PubMed

8. Nitschke L,Carsetti R,Ocker B,Kohler G,Lamers MC CD22 is a negative regulator of B-cell receptor signalling. Curr Biol 1997 7:133 PubMed

9. Powell LD,Varki A I-type lectins. J Biol Chem 1995 270:14243 PubMed

10. Stamenkovic I,Seed B The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion. Nature 1990 345:74 PubMed

11. Tuscano JM,Engel P,Tedder TF,Agarwal A,Kehrl JH Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22. Eur J Immunol 1996 26:1246 PubMed

12. Wilson GL,Fox CH,Fauci AS,Kehrl JH cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions. J Exp Med 1991 173:137 PubMed

13. Wilson GL,Najfeld V,Kozlow E,Menniger J,Ward D,Kehrl JH Genomic structure and chromosomal mapping of the human CD22 gene. J Immunol 1993 150:5013 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov