|CD21||CR2 (complement receptor type 2), EBV-receptor(Epstein Barr virus receptor), C3δ-receptor, gp140|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
Marginal zone cell
|130 / 130|
145 / 145
|CD21 is expressed on mature B cells with strong expression in marginal zone cells, moderate expression by follicular mantle zone B cells and no expression by germinal centre B cells. B cells are on the stage when surface Ig is first expressed but is lost upon activation. CD21 is also expressed on follicular dendritic cells and a subset of immature thymocytes. Low density expression is detected on pharyngeal and cervical epithelial cells, fetal astrocytes, subsets of immature and normal thymocytes, T cells and T-ALL. Some anti-CD21 mAbs bind epithelial cells.|
|MOLECULAR FAMILY NAME: Belongs to the regulators of complement activation gene family.|
CD21 is a single-pass type-1 glycoprotein. It contains an extracellular domain which contains 15-16 short consensus repeats (SCR), with 15 to 16 complement control protein (CCP) domains tightly-folded units of about 60 aa which are organized in at least 5 groups, that forms a minimum of 6 different epitopes, a 28 aa transmembrane domain and 34 aa C-terminal cytoplasmic tail containing potential protein kinases C and tyrosine kinase sites. The CD21 gene is a member of the regulation of complement activation (RCA) gene cluster that encodes a family of C3/C4 binding proteins (see CD35). SCR 1 and 2 have binding sites for C3 fragments and EBV that although distinct probably overlap. SCR 3 and 4 bind soluble cross-linked C3δγ with high affinity. CSR 5-8 have two distinct epitopes recognized by different mAbs.
Alternative splicing yields 4 different isoforms. SCR1 and 2 have binding sites for C3 fragments and EBV that probably overlap. SCR3 and 4 bind soluble cross-linked C3δγ with high affinity. SCR 5-8 have two distinct epitopes recognized by different mAbs. The extra CCP at position 11 is supposed to be the product of alternative splicing.
SCR 5-8 is suggested to be glycosylated, a N-linked oligosaccharide.
|CD21 is a receptor for the C3 activation fragments iC3b and C3δ. It is also the receptor used by the Epstein-Barr virus (EBV) to infect B lymphocytes. CD21 has been shown to bind CD23 and IFNa. CD21 is also associated with CD35 on B cells.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD21
|CD21 is a complement receptor 2 for Epstein Barr virus receptor (EBV), for C3δ, C3δγ, iC3b and binds to the breakdown products of the C3 complement component and may activate B cells through CD21. CD21 is part of a large signal-transduction complex that also involves CD19, CD81, and Leu 13. IgM acts with CD21 in B cell activation. High density expression on marginal B cells enables a rapid primary immune response in particular to T-cell independent antigens. Co-valent antigen-complement complexes bind to the B cell antigen receptor, the BCR surface Ig, the simultaneous interaction of CD21 with the complement component C3δ enhances signaling through the BCR. The CD21 signal, which is transduced through the associated molecules CD19 and CD81, very effectively lowers the activation threshold of the BCR. Thus C3δ may be considered as a molecular adjuvant that directs the acquired immune response toward antigens recognized by the innate immune response. Mice made defective in CD21 have an impaired immune response to T-dependent antigens. The CD21/CD23 interaction may have a regulatory role in IgE production. The murine knockouts show an important function of CD21 on B cells in both T cell-dependent and type 2 T-cell independent responses.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD21 IN INTACT ANIMAL
CD21 is a surface marker useful in phenotypying malignant B-cell lymphomas and for immunohistologic study of follicular dendtritic cell patterns. The combined demonstration of EBV and CD21 is used in the diagnosis of post-transplant lymphoproliferative disease. The inability of infants below the age of two to make adequate antibody responses to polysaccharides is associated with the lack of CD21+ marginal zone B cells.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD21: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD21: No information.
The high density of CD21 on splenic marginal zone B-cells suggests the possibility for rapid and easy activation in a primary immune response. CD21 appears crucial in TI-1 response as for pneumococcal polysaccharides.
Database accession numbers
Revised June 25, 2008