PROW: CD21

PROW and IWHLDA present the GUIDE on:
CD21
Author: Wim Timens
Reviewer: Erwin W. Gelfand
Link to additional info in FORUM [GUIDE BAR]

ALTERNATE NAMES FOR CD21

C3d receptor
CR2
Epstein Barr virus receptor, EBV-R

MAJOR LINKS FOR CD21

NCBI LocusLink Record: 1380
Mendelian Inheritance in Man (OMIM): 120650
SwissProt annotated protein record: P20023

FUNCTION BIOCHEMICAL ACTIVITY OF CD21 - No information

CELLULAR FUNCTION OF CD21 Link to additional info in FORUM

Receptor for EBV and for C3d, C3dg and iC3b
Complement components may activate B cells through CD21. CD21 is part of a large signal-transduction complex that also involves CD19, CD81, and Leu13

DISEASE RELEVANCE OF CD21 AND FUNCTION OF CD21 IN INTACT ANIMAL - Typing of lymphomas

STRUCTURE MOLECULAR FAMILY FOR CD21

Families in which CD21 is a member
- CD21-->regulators of complement activation gene

MOLECULAR STRUCTURE OF CD21

The extracellular region consists of multiple short consensus repeats, tightly-folded units of about 60 residues, organized in at least five groups, supposed to comprise at least six different epitopes
28 amino-acid transmembrane domain
34 amino-acid C-terminal cytoplasmic tail
The cytoplasmic region contains potential protein kinase C and tyrosine kinase sites

MOLECULAR MASS OF CD21

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
B cells	145 kDa,	110kDa after endoglycosidase F treatment
Soluble	130 kDa

POST-TRANSCRIPTIONAL MODIFICATION OF CD21

Extra CCP at position 11 is supposed to be the product of alternative splicing

POST-TRANSLATIONAL MODIFICATION OF CD21

SCR 5-8 is suggested to be glycosylated (N-linked oligosaccharide)

MOLECULAR INTERACTIONS PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD21 - No information

SUBSTRATES FOR CD21 - No information

ENZYMES WHICH MODIFY CD21 - No information

LIGANDS FOR CD21 AND MOLECULES ASSOCIATED WITH CD21

MOLECULE	COMMENT
C3d	Ligand whose binding site located at SCR 1-2 (epitope different from Epstein Barr Virus [EBV])
Soluble crosslinked C3dg	SCR 3-4 necessary for high affinity binding of C3dg
CD23	Ligand whose binding site located at SCR 5-8
CD19	See note 1
CD81	See note 1
Leu13	See note 1
Molecule on EBV	Ligand whose binding site is located at SCR 1-2

Note 1 - CD19, CD21, CD81 and Leu 13 form a signaling complex; ligands to CD21 can strongly enhance activation by this complex

EXPRESSION MAIN CELLULAR EXPRESSION OF CD21

B cells, from the stage when surface Ig was first expressed, then lost upon activation
Stains follicular mantle zone B cells and marginal zone B cells, the latter strongly
Follicular dendritic cells
Subset of immature thymocytes*
Some mAb bind epithelial tissue

AUTHOR'S ADDITIONAL INSIGHTS ON CD21

The high density of CD21 on (splenic) marginal zone B-cells suggests possibility for rapid and easy activation in a primary immune response
CD21 appears crucial in TI-2 response (as for pneumococcal polysaccharides)

REAGENTS CD21-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
LT21	A Filatov, Moscow, Rus
BU80 aka	DL Hardie, Birmingham, UK
BU37	DL Hardie, Birmingham, UK
BU79	DL Hardie, Birmingham, UK
BU81	DL Hardie, Birmingham, UK
DR53	G Delsol, Toulouse, Fr
5D1	W Zeijlemaker, Amsterdam, NL

SELECTION OF OTHER CD21-SPECIFIC REFERENCE MAB

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
B2	Nadler, 1981
HB5	Tedder, 1984
OKB7	Knowles, 1984
BU33	Ling, 1994
1F8	Petzer, 1988
5A10	Carel 1990

Each antibody listed is represented by a different epitope

SELECTED REFERENCES ON CD21

REVIEWS

1. Cooper NR,Moore MD,Nemerow GR Immunobiology of CR2, the B lymphocyte receptor for Epstein-Barr virus and the C3d complement fragment. Annu Rev Immunol 1988 6:85 PubMed

2. Fearon DT The CD19-CR2-TAPA-1 complex, CD45 and signaling by the antigen receptor of B lymphocytes. Curr Opin Immunol 1993 5:341 PubMed

PRIMARY CITATIONS

3. Carel JC,Myones BL,Frazier B,Holers VM Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection. J Biol Chem 1990 265:12293 PubMed

4. Knowles DM 2d,Tolidjian B,Marboe CC,Mittler RS,Talle MA,Goldstein G Distribution of antigens defined by OKB monoclonal antibodies on benign and malignant lymphoid cells and on nonlymphoid tissues. Blood 1984 63:886 PubMed

5. Ling NR,Brown B,Hardie D Synergy test for recognition of epitopes on soluble proteins; its application in the study of CD21 and CD23 antigens and their respective antibodies. J Immunol Methods 1994 173:11 PubMed

6. Nadler LM,Stashenko P,Hardy R,van Agthoven A,Terhorst C,Schlossman SF Characterization of a human B cell-specific antigen (B2) distinct from J Immunol 1981 126:1941 PubMed

7. Paterson RL,Kelleher CA,Streib JE,Amankonah TD,Xu JW,Jones JF,Gelfand EW Activation of human thymocytes after infection by EBV. J Immunol 1995 154:1440 ** PubMed

8. Petzer AL,Schulz TF,Stauder R,Eigentler A,Myones BL,Dierich MP Structural and functional analysis of CR2/EBV receptor by means of monoclonal antibodies and limited tryptic digestion. Immunology 1988 63:47 PubMed

9. Tedder TF,Clement LT,Cooper MD Expression of C3d receptors during human B cell differentiation: immunofluorescence analysis with the HB-5 monoclonal antibody. J Immunol 1984 133:678 PubMed

WWW RESOURCES

* indicates ammended by reviewer, ** indicates added by reviewer

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