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{{Infobox_gene}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
'''Complement receptor type 2''' (CR2), also known as '''complement C3d receptor''', '''Epstein-Barr virus receptor''', and '''CD21''' (cluster of differentiation 21), is a [[protein]] that in humans is encoded by the CR2 [[gene]].
{{GNF_Protein_box
| image = PBB_Protein_CR2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ghq.
| PDB = {{PDB2|1ghq}}, {{PDB2|1ly2}}, {{PDB2|1w2r}}, {{PDB2|1w2s}}, {{PDB2|2gsx}}
| Name = Complement component (3d/Epstein Barr virus) receptor 2
| HGNCid = 2336
| Symbol = CR2
| AltSymbols =; C3DR; CD21
| OMIM = 120650
| ECnumber = 
| Homologene = 55611
| MGIid = 88489
| GeneAtlas_image1 = PBB_GE_CR2_205544_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004875 |text = complement receptor activity}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006958 |text = complement activation, classical pathway}} {{GNF_GO|id=GO:0045087 |text = innate immune response}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1380
    | Hs_Ensembl = ENSG00000117322
    | Hs_RefseqProtein = NP_001006659
    | Hs_RefseqmRNA = NM_001006658
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 205694198
    | Hs_GenLoc_end = 205729863
    | Hs_Uniprot = P20023
    | Mm_EntrezGene = 12902
    | Mm_Ensembl = ENSMUSG00000026616
    | Mm_RefseqmRNA = NM_007758
    | Mm_RefseqProtein = NP_031784
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 196841897
    | Mm_GenLoc_end = 196877439
    | Mm_Uniprot = Q6LAP4
  }}
}}


'''Complement component (3d/Epstein Barr virus) receptor 2''', also known as '''CR2''' and '''CD21''', is a protein involved in the [[complement system]]. It binds to [[C3d]]. [[B cell|B cells]] have CR2 receptors on their surfaces, allowing the complement system to play a role in B-cell activation and maturation <ref name="entrez">{{cite web | title = Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1380| accessdate = }}</ref>
CR2 is involved in the [[complement system]]. It binds to iC3b (inactive derivative of C3b), C3dg, or C3d.<ref name=Frank>Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor H. eds. ''Samter's Immunologic Diseases, 6th ed. Vol. 1,'' p. 281-298, Philadelphia: Lippincott Williams & Wilkins, {{ISBN|0-7817-2120-2}}.</ref> [[B cell]]s have CR2 receptors on their surfaces, allowing the complement system to play a role in B-cell activation and maturation <ref name="entrez_ 1380">{{cite web | title = Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1380| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Interactions==
{{PBB_Summary
 
| section_title =  
CR2 on mature B cells form a complex with two other membrane proteins, [[CD19]] and [[CD81]](=TAPA-1). The CR2-CD19-CD81 complex is often called the B cell coreceptor complex,<ref name=Abbas>Abbas AK, Lichtman AH (2003). ''Cellular and Molecular Immunology, 5th ed.'' Philadelphia: Saunders, {{ISBN|0-7216-0008-5}}</ref> because CR2 binds to antigens through attached C3d (or iC3b or C3dg) when the membrane IgM binds to the antigen. This results in the B cell having greatly enhanced response to the antigen.<ref name=Frank/>
| summary_text = Complement component receptor-2 (CR2) is the membrane protein on B lymphocytes to which the Epstein-Barr virus (EBV) binds during infection of these cells. See also MIM 120620. Yefenof et al. (1976) found complete overlapping of EBV receptors and C3 (MIM 120700) receptors on human B lymphocytes.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1380| accessdate = }}</ref>
 
}}
Complement receptor 2 has been shown to [[Protein-protein interaction|interact]] with CD19.<ref name="pmid1383329">{{cite journal |vauthors=Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF | title = The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules | journal = J. Immunol. | volume = 149 | issue = 9 | pages = 2841–50 |date=November 1992 | pmid = 1383329 | doi = }}</ref><ref name="pmid9804823">{{cite journal |vauthors=Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E | title = CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82 | journal = J. Biol. Chem. | volume = 273 | issue = 46 | pages = 30537–43 |date=November 1998 | pmid = 9804823 | doi = 10.1074/jbc.273.46.30537 }}</ref>
 
[[Epstein-Barr virus]] (EBV) binds to B cells at CR2 during infection of these cells. Yefenof et al. (1976) found complete overlapping of EBV receptors and [[Complement component 3|C3]] receptors on human B cells.<ref name="entrez_ 1380"/><ref name="pmid181330">{{cite journal |vauthors=Yefenof E, Klein G, Jondal M, Oldstone MB | title = Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines | journal = Int. J. Cancer | volume = 17 | issue = 6 | pages = 693–700 |date=June 1976 | pmid = 181330 | doi = 10.1002/ijc.2910170602| url =  }}</ref>
 
==Isoforms==
 
The canonical Cr2/CD21 gene of subprimate mammals produces two types of complement receptor (CR1, ca. 200 kDa; CR2, ca. 145 kDa) via alternative mRNA splicing. The murine Cr2 gene contains 25 exons; a common first exon is spliced to exon 2 and to exon 9 in transcripts encoding CR1 and CR2, respectively. A transcript with an [[open reading frame]] of 4,224 nucleotides encodes the long isoform, CR1; this is predicted to be a protein of 1,408 amino acids that includes 21 short consensus repeats (SCR) of ca. 60 amino acids each, plus transmembrane and cytoplasmic regions. Isoform CR2 (1,032 amino acids) is encoded by a shorter transcript (3,096 coding nucleotides) that lacks exons 2-8 encoding SCR1-6. CR1 and CR2 on murine B cells form complexes with a co-accessory activation complex containing CD19, CD81, and the fragilis/Ifitm (murine equivalents of LEU13) proteins.<ref name="pmid18713965">{{cite journal |vauthors=Jacobson AC, Weis JH | title = Comparative functional evolution of human and mouse CR1 and CR2 | journal = J. Immunol. | volume = 181 | issue = 5 | pages = 2953–9 |date=September 2008 | pmid = 18713965 | pmc = 3366432 | doi=10.4049/jimmunol.181.5.2953}}</ref>
 
The CR2 gene of primates produces only the smaller isoform, CR2; primate [[complement receptor 1]], which recapitulates many of the structural domains and presumed functions of Cr2-derived CR1 in subprimates, is encoded by a distinct CR1 gene (apparently derived from the gene Crry of subprimates).
 
Isoforms CR1 and CR2 derived from the non-primate Cr2 locus possess the same C-terminal sequence, such that association with and activation through CD19 should be equivalent. CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein produced primarily by [[follicular dendritic cell]]s, appears to be critical for generation of appropriately activated B cells of the germinal centre and for mature antibody responses to bacterial infection.<ref name="pmid23733878">{{cite journal |vauthors=Donius LR, Handy JM, Weis JJ, Weis JH | title = Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1 | journal = J. Immunol. | volume = 191 | issue = 1 | pages = 434–47 |date=July 2013 | pmid = 23733878 | doi = 10.4049/jimmunol.1203176 | pmc=3707406}}</ref>
 
==Immunohistochemistry==
Although CR2 is present on all mature B-cells and follicular dendritic cells (FDCs), this becomes readily apparent only when [[immunohistochemistry]] is performed on [[frozen section procedure|frozen sections]]. In more conventional paraffin-embedded tissue samples, only the FDCs retain the staining pattern. As a result, CR2, more commonly called CD21 in the context of immunohistochemistry, can be used to demonstrate the FDC meshwork in lymphoid tissue.
 
This feature can be useful in examining tissue where the normal [[germinal centre]]s have been effaced by disease processes, such as [[HIV]] infection. The pattern of the FDC meshwork may also be altered in some [[neoplasm|neoplastic]] conditions, such as B-cell [[MALT lymphoma]]s, [[mantle cell lymphoma]], and some [[T cell lymphoma]]s. [[Castleman's disease]] is typified by the presence of abnormal FDCs, and both this, and malignant FDC tumours may therefore be demonstrated using CR2/CD21 antibodies.<ref name=Leong>{{cite book|author=Leong, Anthony S-Y|author2=Cooper, Kumarason|author3=Leong, F Joel W-M|year=2003|title=Manual of Diagnostic Cytology|edition=2|publisher=Greenwich Medical Media, Ltd.|pages=93–94|isbn=1-84110-100-1}}</ref>
{{Clear}}


==References==
==References==
{{reflist|2}}
{{reflist|35em}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|35em}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Cooper NR, Bradt BM, Rhim JS, Nemerow GR |title=CR2 complement receptor. |journal=J. Invest. Dermatol. |volume=94 |issue= 6 Suppl |pages= 112S?117S |year= 1990 |pmid= 2161885 |doi=10.1111/1523-1747.ep12876069 }}
| citations =
*{{cite journal  |vauthors=Gauffre A, Viron A, Barel M |title=Nuclear localization of the Epstein-Barr virus/C3d receptor (CR2) in the human Burkitt B lymphoma cell, Raji. |journal=Mol. Immunol. |volume=29 |issue= 9 |pages= 1113–20 |year= 1992 |pmid= 1323059 |doi=10.1016/0161-5890(92)90044-X |display-authors=etal}}
*{{cite journal  | author=Cooper NR, Bradt BM, Rhim JS, Nemerow GR |title=CR2 complement receptor. |journal=J. Invest. Dermatol. |volume=94 |issue= 6 Suppl |pages= 112S-117S |year= 1990 |pmid= 2161885 |doi=  }}
*{{cite journal  |vauthors=Levy E, Ambrus J, Kahl L |title=T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE). |journal=Clin. Exp. Immunol. |volume=90 |issue= 2 |pages= 235–44 |year= 1992 |pmid= 1424280 |doi=  10.1111/j.1365-2249.1992.tb07935.x| pmc=1554594  |display-authors=etal}}
*{{cite journal  | author=Yefenof E, Klein G, Jondal M, Oldstone MB |title=Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines. |journal=Int. J. Cancer |volume=17 |issue= 6 |pages= 693-700 |year= 1976 |pmid= 181330 |doi=  }}
*{{cite journal  |vauthors=Matsumoto AK, Kopicky-Burd J, Carter RH |title=Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. |journal=J. Exp. Med. |volume=173 |issue= 1 |pages= 55–64 |year= 1991 |pmid= 1702139 |doi=10.1084/jem.173.1.55  | pmc=2118751  |display-authors=etal}}
*{{cite journal  | author=Gauffre A, Viron A, Barel M, ''et al.'' |title=Nuclear localization of the Epstein-Barr virus/C3d receptor (CR2) in the human Burkitt B lymphoma cell, Raji. |journal=Mol. Immunol. |volume=29 |issue= 9 |pages= 1113-20 |year= 1992 |pmid= 1323059 |doi=  }}
*{{cite journal  |vauthors=Tuveson DA, Ahearn JM, Matsumoto AK, Fearon DT |title=Molecular interactions of complement receptors on B lymphocytes: a CR1/CR2 complex distinct from the CR2/CD19 complex. |journal=J. Exp. Med. |volume=173 |issue= 5 |pages= 1083–9 |year= 1991 |pmid= 1708808 |doi=10.1084/jem.173.5.1083  | pmc=2118840 }}
*{{cite journal  | author=Bradbury LE, Kansas GS, Levy S, ''et al.'' |title=The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. |journal=J. Immunol. |volume=149 |issue= 9 |pages= 2841-50 |year= 1992 |pmid= 1383329 |doi= }}
*{{cite journal  |vauthors=Kalli KR, Ahearn JM, Fearon DT |title=Interaction of iC3b with recombinant isotypic and chimeric forms of CR2. |journal=J. Immunol. |volume=147 |issue= 2 |pages= 590–4 |year= 1991 |pmid= 1830068 |doi=  }}
*{{cite journal  | author=Levy E, Ambrus J, Kahl L, ''et al.'' |title=T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE). |journal=Clin. Exp. Immunol. |volume=90 |issue= 2 |pages= 235-44 |year= 1992 |pmid= 1424280 |doi=  }}
*{{cite journal  |vauthors=Barel M, Gauffre A, Lyamani F |title=Intracellular interaction of EBV/C3d receptor (CR2) with p68, a calcium-binding protein present in normal but not in transformed B lymphocytes. |journal=J. Immunol. |volume=147 |issue= 4 |pages= 1286–91 |year= 1991 |pmid= 1831222 |doi=  |display-authors=etal}}
*{{cite journal  | author=Matsumoto AK, Kopicky-Burd J, Carter RH, ''et al.'' |title=Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. |journal=J. Exp. Med. |volume=173 |issue= 1 |pages= 55-64 |year= 1991 |pmid= 1702139 |doi=  }}
*{{cite journal  |vauthors=Delcayre AX, Salas F, Mathur S |title=Epstein Barr virus/complement C3d receptor is an interferon alpha receptor. |journal=EMBO J. |volume=10 |issue= 4 |pages= 919–26 |year= 1991 |pmid= 1849076 |doi=  | pmc=452735  |display-authors=etal}}
*{{cite journal  | author=Tuveson DA, Ahearn JM, Matsumoto AK, Fearon DT |title=Molecular interactions of complement receptors on B lymphocytes: a CR1/CR2 complex distinct from the CR2/CD19 complex. |journal=J. Exp. Med. |volume=173 |issue= 5 |pages= 1083-9 |year= 1991 |pmid= 1708808 |doi=  }}
*{{cite journal  |vauthors=Kurtz CB, Paul MS, Aegerter M |title=Murine complement receptor gene family. II. Identification and characterization of the murine homolog (Cr2) to human CR2 and its molecular linkage to Crry. |journal=J. Immunol. |volume=143 |issue= 6 |pages= 2058–67 |year= 1989 |pmid= 2528587 |doi=  |display-authors=etal}}
*{{cite journal  | author=Kalli KR, Ahearn JM, Fearon DT |title=Interaction of iC3b with recombinant isotypic and chimeric forms of CR2. |journal=J. Immunol. |volume=147 |issue= 2 |pages= 590-4 |year= 1991 |pmid= 1830068 |doi=  }}
*{{cite journal  |vauthors=Fujisaku A, Harley JB, Frank MB |title=Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor. |journal=J. Biol. Chem. |volume=264 |issue= 4 |pages= 2118–25 |year= 1989 |pmid= 2563370 |doi=  |display-authors=etal}}
*{{cite journal  | author=Barel M, Gauffre A, Lyamani F, ''et al.'' |title=Intracellular interaction of EBV/C3d receptor (CR2) with p68, a calcium-binding protein present in normal but not in transformed B lymphocytes. |journal=J. Immunol. |volume=147 |issue= 4 |pages= 1286-91 |year= 1991 |pmid= 1831222 |doi=  }}
*{{cite journal  |vauthors=Moore MD, Cooper NR, Tack BF, Nemerow GR |title=Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 24 |pages= 9194–8 |year= 1988 |pmid= 2827171 |doi=10.1073/pnas.84.24.9194  | pmc=299719 }}
*{{cite journal  | author=Delcayre AX, Salas F, Mathur S, ''et al.'' |title=Epstein Barr virus/complement C3d receptor is an interferon alpha receptor. |journal=EMBO J. |volume=10 |issue= 4 |pages= 919-26 |year= 1991 |pmid= 1849076 |doi=  }}
*{{cite journal  |vauthors=Weis JJ, Toothaker LE, Smith JA |title=Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins. |journal=J. Exp. Med. |volume=167 |issue= 3 |pages= 1047–66 |year= 1988 |pmid= 2832506 |doi=10.1084/jem.167.3.1047  | pmc=2188894 |display-authors=etal}}
*{{cite journal  | author=Kurtz CB, Paul MS, Aegerter M, ''et al.'' |title=Murine complement receptor gene family. II. Identification and characterization of the murine homolog (Cr2) to human CR2 and its molecular linkage to Crry. |journal=J. Immunol. |volume=143 |issue= 6 |pages= 2058-67 |year= 1989 |pmid= 2528587 |doi=  }}
*{{cite journal  |vauthors=Weis JJ, Fearon DT, Klickstein LB |title=Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 15 |pages= 5639–43 |year= 1986 |pmid= 3016712 |doi=10.1073/pnas.83.15.5639  | pmc=386344 |display-authors=etal}}
*{{cite journal  | author=Fujisaku A, Harley JB, Frank MB, ''et al.'' |title=Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor. |journal=J. Biol. Chem. |volume=264 |issue= 4 |pages= 2118-25 |year= 1989 |pmid= 2563370 |doi=  }}
*{{cite journal  |vauthors=Weis JH, Morton CC, Bruns GA |title=A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32. |journal=J. Immunol. |volume=138 |issue= 1 |pages= 312–5 |year= 1987 |pmid= 3782802 |doi=  |display-authors=etal}}
*{{cite journal  | author=Moore MD, Cooper NR, Tack BF, Nemerow GR |title=Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 24 |pages= 9194-8 |year= 1988 |pmid= 2827171 |doi=  }}
*{{cite journal  |vauthors=Aubry JP, Pochon S, Gauchat JF |title=CD23 interacts with a new functional extracytoplasmic domain involving N-linked oligosaccharides on CD21. |journal=J. Immunol. |volume=152 |issue= 12 |pages= 5806–13 |year= 1994 |pmid= 7515913 |doi=  |display-authors=etal}}
*{{cite journal  | author=Weis JJ, Toothaker LE, Smith JA, ''et al.'' |title=Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins. |journal=J. Exp. Med. |volume=167 |issue= 3 |pages= 1047-66 |year= 1988 |pmid= 2832506 |doi=  }}
*{{cite journal  |vauthors=Matsumoto AK, Martin DR, Carter RH |title=Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. |journal=J. Exp. Med. |volume=178 |issue= 4 |pages= 1407–17 |year= 1993 |pmid= 7690834 |doi=10.1084/jem.178.4.1407 | pmc=2191213  |display-authors=etal}}
*{{cite journal  | author=Weis JJ, Fearon DT, Klickstein LB, ''et al.'' |title=Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 15 |pages= 5639-43 |year= 1986 |pmid= 3016712 |doi=  }}
*{{cite journal  |vauthors=Barel M, Balbo M, Gauffre A, Frade R |title=Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein. |journal=Mol. Immunol. |volume=32 |issue= 6 |pages= 389–97 |year= 1995 |pmid= 7753047 |doi=10.1016/0161-5890(95)00005-Y }}
*{{cite journal  | author=Weis JH, Morton CC, Bruns GA, ''et al.'' |title=A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32. |journal=J. Immunol. |volume=138 |issue= 1 |pages= 312-5 |year= 1987 |pmid= 3782802 |doi=  }}
*{{cite journal  | author=Aubry JP, Pochon S, Gauchat JF, ''et al.'' |title=CD23 interacts with a new functional extracytoplasmic domain involving N-linked oligosaccharides on CD21. |journal=J. Immunol. |volume=152 |issue= 12 |pages= 5806-13 |year= 1994 |pmid= 7515913 |doi= }}
*{{cite journal  | author=Matsumoto AK, Martin DR, Carter RH, ''et al.'' |title=Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. |journal=J. Exp. Med. |volume=178 |issue= 4 |pages= 1407-17 |year= 1993 |pmid= 7690834 |doi=  }}
*{{cite journal  | author=Barel M, Balbo M, Gauffre A, Frade R |title=Binding sites of the Epstein-Barr virus and C3d receptor (CR2, CD21) for its three intracellular ligands, the p53 anti-oncoprotein, the p68 calcium binding protein and the nuclear p120 ribonucleoprotein. |journal=Mol. Immunol. |volume=32 |issue= 6 |pages= 389-97 |year= 1995 |pmid= 7753047 |doi= }}
}}
{{refend}}
{{refend}}
==See also==
* [[Epstein Barr virus]]


==External links==
==External links==
* {{MeshName|Complement+Receptors+2}}
* {{MeshName|Complement+Receptors+2}}


{{protein-stub}}
{{PDB Gallery|geneid=1380}}
{{Complement system}}
{{Complement system}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{Immunoglobulin superfamily immune receptors}}
[[Category:Complement system]]
[[Category:Complement system]]

Latest revision as of 00:00, 29 October 2017

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Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of differentiation 21), is a protein that in humans is encoded by the CR2 gene.

CR2 is involved in the complement system. It binds to iC3b (inactive derivative of C3b), C3dg, or C3d.[1] B cells have CR2 receptors on their surfaces, allowing the complement system to play a role in B-cell activation and maturation [2]

Interactions

CR2 on mature B cells form a complex with two other membrane proteins, CD19 and CD81(=TAPA-1). The CR2-CD19-CD81 complex is often called the B cell coreceptor complex,[3] because CR2 binds to antigens through attached C3d (or iC3b or C3dg) when the membrane IgM binds to the antigen. This results in the B cell having greatly enhanced response to the antigen.[1]

Complement receptor 2 has been shown to interact with CD19.[4][5]

Epstein-Barr virus (EBV) binds to B cells at CR2 during infection of these cells. Yefenof et al. (1976) found complete overlapping of EBV receptors and C3 receptors on human B cells.[2][6]

Isoforms

The canonical Cr2/CD21 gene of subprimate mammals produces two types of complement receptor (CR1, ca. 200 kDa; CR2, ca. 145 kDa) via alternative mRNA splicing. The murine Cr2 gene contains 25 exons; a common first exon is spliced to exon 2 and to exon 9 in transcripts encoding CR1 and CR2, respectively. A transcript with an open reading frame of 4,224 nucleotides encodes the long isoform, CR1; this is predicted to be a protein of 1,408 amino acids that includes 21 short consensus repeats (SCR) of ca. 60 amino acids each, plus transmembrane and cytoplasmic regions. Isoform CR2 (1,032 amino acids) is encoded by a shorter transcript (3,096 coding nucleotides) that lacks exons 2-8 encoding SCR1-6. CR1 and CR2 on murine B cells form complexes with a co-accessory activation complex containing CD19, CD81, and the fragilis/Ifitm (murine equivalents of LEU13) proteins.[7]

The CR2 gene of primates produces only the smaller isoform, CR2; primate complement receptor 1, which recapitulates many of the structural domains and presumed functions of Cr2-derived CR1 in subprimates, is encoded by a distinct CR1 gene (apparently derived from the gene Crry of subprimates).

Isoforms CR1 and CR2 derived from the non-primate Cr2 locus possess the same C-terminal sequence, such that association with and activation through CD19 should be equivalent. CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein produced primarily by follicular dendritic cells, appears to be critical for generation of appropriately activated B cells of the germinal centre and for mature antibody responses to bacterial infection.[8]

Immunohistochemistry

Although CR2 is present on all mature B-cells and follicular dendritic cells (FDCs), this becomes readily apparent only when immunohistochemistry is performed on frozen sections. In more conventional paraffin-embedded tissue samples, only the FDCs retain the staining pattern. As a result, CR2, more commonly called CD21 in the context of immunohistochemistry, can be used to demonstrate the FDC meshwork in lymphoid tissue.

This feature can be useful in examining tissue where the normal germinal centres have been effaced by disease processes, such as HIV infection. The pattern of the FDC meshwork may also be altered in some neoplastic conditions, such as B-cell MALT lymphomas, mantle cell lymphoma, and some T cell lymphomas. Castleman's disease is typified by the presence of abnormal FDCs, and both this, and malignant FDC tumours may therefore be demonstrated using CR2/CD21 antibodies.[9]

References

  1. ↑ 1.0 1.1 Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor H. eds. Samter's Immunologic Diseases, 6th ed. Vol. 1, p. 281-298, Philadelphia: Lippincott Williams & Wilkins, ISBN 0-7817-2120-2.
  2. ↑ 2.0 2.1 "Entrez Gene: CR2 complement component (3d/Epstein Barr virus) receptor 2".
  3. ↑ Abbas AK, Lichtman AH (2003). Cellular and Molecular Immunology, 5th ed. Philadelphia: Saunders, ISBN 0-7216-0008-5
  4. ↑ Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (November 1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". J. Immunol. 149 (9): 2841–50. PMID 1383329.
  5. ↑ Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (November 1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". J. Biol. Chem. 273 (46): 30537–43. doi:10.1074/jbc.273.46.30537. PMID 9804823.
  6. ↑ Yefenof E, Klein G, Jondal M, Oldstone MB (June 1976). "Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines". Int. J. Cancer. 17 (6): 693–700. doi:10.1002/ijc.2910170602. PMID 181330.
  7. ↑ Jacobson AC, Weis JH (September 2008). "Comparative functional evolution of human and mouse CR1 and CR2". J. Immunol. 181 (5): 2953–9. doi:10.4049/jimmunol.181.5.2953. PMC 3366432. PMID 18713965.
  8. ↑ Donius LR, Handy JM, Weis JJ, Weis JH (July 2013). "Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1". J. Immunol. 191 (1): 434–47. doi:10.4049/jimmunol.1203176. PMC 3707406. PMID 23733878.
  9. ↑ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 93–94. ISBN 1-84110-100-1.

Further reading

External links

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