CD21

同

CR2

発現細胞

• 成熟B細胞

分子量

• 145 kDa

機能

• 補体成分のC3dやEBウイルスの受容体。CD19,CD21,CD81はB細胞のコレセプターを構成

ファミリー

• complement control protein (CCP)

同

CR2, Epstein-Barr virus receptor, C3d receptor

同

CR2

PrepTutorEJDIC

1. certificate of deposit / (また『C.D.』)Civil Defense民間防衛

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/04/03 06:25:43」(JST)

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CR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GHQ, 1LY2, 1W2R, 1W2S, 2GSX, 3OED
Identifiers
Aliases	CR2, C3DR, CD21, CR, CVID7, SLEB9, complement component 3d receptor 2, complement C3d receptor 2
External IDs	MGI: 88489 HomoloGene: 55611 GeneCards: CR2
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.2 Start 207,454,230 bp End 207,489,895 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 H6|1 98.44 cM Start 195,136,811 bp End 195,176,716 bp
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • protein homodimerization activity • virus receptor activity • complement binding • transmembrane signaling receptor activity • complement receptor activity • protein binding Cellular component • integral component of membrane • membrane • receptor complex • extracellular exosome • plasma membrane Biological process • immune system process • B cell proliferation • immune response • complement activation, classical pathway • viral entry into host cell • B cell differentiation • innate immune response • viral process • complement receptor mediated signaling pathway • signal transduction • regulation of complement activation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1380	12902
Ensembl	ENSG00000117322	ENSMUSG00000026616
UniProt	P20023	P19070
RefSeq (mRNA)	NM_001006658 NM_001877	NM_007758
RefSeq (protein)	NP_001006659 NP_001868	n/a
Location (UCSC)	Chr 1: 207.45 – 207.49 Mb	Chr 1: 195.14 – 195.18 Mb
PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. B cells have CR2 receptors on their surfaces, allowing the complement system to play a role in B-cell activation and maturation

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, 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.

Complement receptor 2 has been shown to interact with CD19.

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.

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.

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.

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.

Further reading

• Cooper NR, Bradt BM, Rhim JS, Nemerow GR (1990). "CR2 complement receptor". J. Invest. Dermatol. 94 (6 Suppl): 112S?117S. doi:10.1111/1523-1747.ep12876069. PMID 2161885. 
• Gauffre A, Viron A, Barel M, et al. (1992). "Nuclear localization of the Epstein-Barr virus/C3d receptor (CR2) in the human Burkitt B lymphoma cell, Raji". Mol. Immunol. 29 (9): 1113–20. doi:10.1016/0161-5890(92)90044-X. PMID 1323059. 
• Levy E, Ambrus J, Kahl L, et al. (1992). "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)". Clin. Exp. Immunol. 90 (2): 235–44. doi:10.1111/j.1365-2249.1992.tb07935.x. PMC 1554594 . PMID 1424280. 
• Matsumoto AK, Kopicky-Burd J, Carter RH, et al. (1991). "Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19". J. Exp. Med. 173 (1): 55–64. doi:10.1084/jem.173.1.55. PMC 2118751 . PMID 1702139. 
• Tuveson DA, Ahearn JM, Matsumoto AK, Fearon DT (1991). "Molecular interactions of complement receptors on B lymphocytes: a CR1/CR2 complex distinct from the CR2/CD19 complex". J. Exp. Med. 173 (5): 1083–9. doi:10.1084/jem.173.5.1083. PMC 2118840 . PMID 1708808. 
• Kalli KR, Ahearn JM, Fearon DT (1991). "Interaction of iC3b with recombinant isotypic and chimeric forms of CR2". J. Immunol. 147 (2): 590–4. PMID 1830068. 
• Barel M, Gauffre A, Lyamani F, et al. (1991). "Intracellular interaction of EBV/C3d receptor (CR2) with p68, a calcium-binding protein present in normal but not in transformed B lymphocytes". J. Immunol. 147 (4): 1286–91. PMID 1831222. 
• Delcayre AX, Salas F, Mathur S, et al. (1991). "Epstein Barr virus/complement C3d receptor is an interferon alpha receptor". EMBO J. 10 (4): 919–26. PMC 452735 . PMID 1849076. 
• Kurtz CB, Paul MS, Aegerter M, et al. (1989). "Murine complement receptor gene family. II. Identification and characterization of the murine homolog (Cr2) to human CR2 and its molecular linkage to Crry". J. Immunol. 143 (6): 2058–67. PMID 2528587. 
• Fujisaku A, Harley JB, Frank MB, et al. (1989). "Genomic organization and polymorphisms of the human C3d/Epstein-Barr virus receptor". J. Biol. Chem. 264 (4): 2118–25. PMID 2563370. 
• Moore MD, Cooper NR, Tack BF, Nemerow GR (1988). "Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 84 (24): 9194–8. doi:10.1073/pnas.84.24.9194. PMC 299719 . PMID 2827171. 
• Weis JJ, Toothaker LE, Smith JA, et al. (1988). "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". J. Exp. Med. 167 (3): 1047–66. doi:10.1084/jem.167.3.1047. PMC 2188894 . PMID 2832506. 
• Weis JJ, Fearon DT, Klickstein LB, et al. (1986). "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". Proc. Natl. Acad. Sci. U.S.A. 83 (15): 5639–43. doi:10.1073/pnas.83.15.5639. PMC 386344 . PMID 3016712. 
• Weis JH, Morton CC, Bruns GA, et al. (1987). "A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32". J. Immunol. 138 (1): 312–5. PMID 3782802. 
• Aubry JP, Pochon S, Gauchat JF, et al. (1994). "CD23 interacts with a new functional extracytoplasmic domain involving N-linked oligosaccharides on CD21". J. Immunol. 152 (12): 5806–13. PMID 7515913. 
• Matsumoto AK, Martin DR, Carter RH, et al. (1993). "Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes". J. Exp. Med. 178 (4): 1407–17. doi:10.1084/jem.178.4.1407. PMC 2191213 . PMID 7690834. 
• Barel M, Balbo M, Gauffre A, Frade R (1995). "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". Mol. Immunol. 32 (6): 389–97. doi:10.1016/0161-5890(95)00005-Y. PMID 7753047. 

External links

• Complement Receptors 2 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 補体系の制御因子および受容体 regulators and receptors of the complement system
• 2. エプスタインバーウイルス（EBウイルス）のウイルス学 virology of epstein barr virus
• 3. 体液性免疫応答 the humoral immune response
• 4. 分類不能型低ガンマグロブリン血症の病因 pathogenesis of common variable immunodeficiency
• 5. バーキットリンパ腫の疫学、臨床症状、病理学的特徴、および診断 epidemiology clinical manifestations pathologic features and diagnosis of burkitt lymphoma

English Journal

• Role of toll-like receptors in primary Sjögren's syndrome with a special emphasis on B-cell maturation within exocrine tissues.

• Guerrier T, Le Pottier L, Devauchelle V, Pers JO, Jamin C, Youinou P.SourceEA2216 Immunology & Pathology and IFR 148 ScinBioS, Université Européenne de Bretagne, Université de Brest, Brest, France.
• Journal of autoimmunity.J Autoimmun.2012 Aug;39(1-2):69-76. Epub 2012 Feb 21.
• Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ), all naïve mature B lymphocytes need tonic signaling to stay alive. We reasoned that the same holds true for those B lymphocytes that proliferate in the salivary glands (SGs) of patients with primary Sjögren's syndrom
• PMID 22357449

• Persistence of a Large Population of Exhausted Monoclonal B cells in Mixed Cryoglobuliemia After the Eradication of Hepatitis C Virus Infection.

• Visentini M, Conti V, Cagliuso M, Siciliano G, Scagnolari C, Casato M, Fiorilli M.SourceDepartment of Clinical Immunology, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy, marcella.visentini@uniroma1.it.
• Journal of clinical immunology.J Clin Immunol.2012 Aug;32(4):729-35. Epub 2012 Mar 2.
• PURPOSE: Functionally exhausted and mostly autoreactive B-cells with a peculiar CD21(low)CD11c(+) phenotype accumulate in several human immunological disorders including common variable immunodeficiency, HIV infection and rheumatoid arthritis. In HCV-associated mixed cryoglobulinemia (MC) there is a
• PMID 22382878

• Characterization of the Inflammatory Response in the Uteri of Cows Infected Naturally by Neospora caninum.

• Orozco MA, Morales E, Salmerón F.SourceDepartamento de Patología Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Avenida Universidad 3000, México, D.F. C.P. 04510, Mexico.
• Journal of comparative pathology.J Comp Pathol.2012 Jul 10. [Epub ahead of print]
• Bovine neosporosis manifests during gestation, when the fetus may be vulnerable to pathogens. Experimental studies of Neospora caninum-infected cattle have been performed, but little is known about the in-utero inflammatory response. The aim of this study was to characterize the inflammatory respons
• PMID 22784781

Japanese Journal

• Potential Immunological Adjuvant of `K-Type CpG-Oligodeoxynucleotides Enhanced the Cell Proliferation and IL-6 mRNA Transcription in Canine B Cells

• KAWARAI Shinpei,SATO Kaoru,HORIGUCHI Anna,KURATA Keigo,KIUCHI Akio,TSUJIMOTO Hajime,SAKAGUCHI Masahiro
• Journal of Veterinary Medical Science 73(2), 177-184, 2011
• … Canine B cells were collected by a magnetic cell isolation method using anti-CD21 antibody. … Transcription of TLR2, TLR4, and TLR9 mRNA on canine CD21+ cells was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). … CpG-ODNs induced dose-dependent proliferation of canine CD21+ cells (P<0.05 compared with control-ODNs) detected by BrdU incorporation. …
• NAID 130000342649

• Characteristics of CD5-Positive Splenic Marginal Zone Lymphoma with Leukemic Manifestation ; Clinical, Flow Cytometry, and Histopathological Findings of 11 Cases

• Kojima Minoru,Sato Eriko,Oshimi Kazuo,Murase Takuhei,Koike Tadashi,Tsunoda Sinichirou,Matsumoto Toshiharu,Marutsuka Kousuke,Ogiya Daisuke,Moriuchi Makiko,Tokunaka Mami,Yara Kikuti Yukie,Kikuchi Tomoki,Nakamura Naoya,Ando Kiyoshi
• Journal of Clinical and Experimental Hematopathology 50(2), 107-112, 2010
• … CD21, 4/4 ; …
• NAID 130000434378

• Hepatic Follicular Dendritic Cell Sarcoma Favorably Controlled by Transcatheter Arterial Chemoembolization

• Tsunemine Hiroko,Akasaka Hiroshi,Kusama Toshiyuki,Fujimoto Koji,Motoyama Arata,Aozasa Katsuyuki,Kodaka Taiichi
• Internal Medicine 49(24), 2703-2707, 2010
• … A 78-year-old woman with multiple tumors in the liver and spleen was diagnosed with follicular dendritic cell (FDC) sarcoma based on the histological picture of splenectomized specimen and its expression of CD21 and CD 23. …
• NAID 130000413431

Related Links

• 抗CD21抗体/サイトメトリー専門Webサイト

CD21. 【CR2】. CD21抗原は、分子量145kDaの膜貫通型糖タンパクで、補体調節 タンパクの遺伝子ファミリーに属します。CD21抗原（CR2）は、C3dおよびEpstein-Barr ウィルス（EBV）のレセプタです。成熟Bリンパ球に存在しますが、Tリンパ球や顆粒球、単 球 ...

• CD21 - 免疫組織データベース～いむーの - 神戸大学

CD21 クローン: 2G9 monoclonal (Novocastra) 希釈倍率: x50 抗原賦活化法：圧力鍋 (上記は北大病理部での条件。抗体は必ずしも全てのメーカーを比較して選択している わけではありませんので、必ずしも"推奨メーカー"という意味ではありません。) ...

• (ﾓﾉｸﾛｰﾅﾙ抗体による)ﾘﾝﾊﾟ球表面ﾏｰｶｰの自動解析CD21

CD21抗原は,分子量145kDaの膜貫通型糖タンパクで補体調節に関与します。通常, 成熟B細胞に存在し,T細胞,単球,顆粒球には存在しません。臨床的には白血病・ リンパ腫を含む細胞の分化及び型分類等に用いられています。

Related Pictures

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★リンクテーブル★

リンク元	「EBウイルス」「表面抗原分類」「CD19」
拡張検索	「CD19:CD21 :CD81」「CD212」「CD210」
関連記事	「CD2」「CD」

「EBウイルス」

　　[★]

英

Epstein-Barr virus, EB virus, EBV

同

エプスタイン-バーウイルス エプスタイン-バー・ウイルス、エプスタイン・バーウイルス

関

EBウイルス感染症、ウイルス

ウイルス学

• ヘルペスウイルス科ガンマヘルペスウイルス亜科リンフェクリプトウイルス属
• 二本鎖DNAウイルス。エンベロープあり。
• ウイルスのレセプターはCD21
• Bリンパ球に潜伏感染

EBV関連抗原

• EA, early antigen
• VCA, virus capsid antigen
• EBNA, EB virus determined nuclear antigen
• LMA, late membrane antigen
• LYDMA, lymphocyte-detected membrane antigen

EBV特異抗体

• VCA抗体
• EA抗体
• EBNA抗体

感染症

• 伝染性単核球症：(小児期の初感染ではかぜ、あるいは不顕性感染(乳幼児では不顕性が多い))
• バーキットリンパ腫：悪性リンパ腫。chr8, chr14の相互転座による染色体異常(BL細胞)c-mycの発現が活性化
• B細胞リンパ腫(HIV感染者など)
• NK細胞リンパ腫(097H066)
• Duncan症候群(XLP)
• 慢性活動性EBV感染症(chronic active EBV infection)
• エイズでの日和見感染。日和見Bリンパ腫
• 上咽頭癌：中国で多い
• 胃癌
• 口腔内白斑

感染経路

• 唾液感染

疫学

• 日本では3歳までに80%が感染する (SMB.530)

検査

• 急性期・回復期に、VCA-IGM, VCA-IgG, EA(早期抗原, early antigen)の高値、EBNA(核内抗原)の陰性を証明

EBNAは感染後3ヶ月以上経たないと立ち上がらない。

• Paul-Bunnel反応(1週間40%, 4週間80-90%)

• ウイルス抗体価：急性期（発病2～7日）と回復期（2～3週）の検体を同時測定し、回復期の抗体価が急性期の結果の4倍（2管差）以上に上昇したとき、血清学的に有意とみなす。

抗体のパターン

	VCA IgG	VCA IgM	EBNA	EA IgG
感染前	ー	ー	ー	ー
急性期	＋	＋	ー	＋／ー
回復期	＋	＋／ー	＋／ー	＋／ー
感染既往	＋	ー	＋	＋／ー
再活性化	＋	＋／ー	＋	＋

目的別検査組み合わせ

	VCA IgG	VCA IgM	EBNA	EA IgG	VCA IgA
伝染性単核症	○	○	○	○
EBV再活性化の疑い	○		○	○
既往確認	○		○
バーキットリンパ腫	○		○	○
上咽頭癌	○		○	○	○
慢性活動性EBV感染症	○			○	○
上記以外でのEBV感染疑い	○	○	○	○

「表面抗原分類」

　　[★]

英

cluster of differentiation, CD

• 細胞の表面抗原を認識する抗体を整理した分類

Bリンパ球 CD10,CD19,CD20

Tリンパ球 CD2,CD3,CD5,CD7

幹細胞 CD34

顆粒球 CD13,CD33

単球 CD14：LPSをリガンドとし、Toll-like receptorと共役して細胞内シグナルを伝達する分子。

巨核球 CD41(GpIIb),CD42(GpIb)

NK細胞：CD16(IgGのFc部に対する受容体)、CD56(NCAM-I)

CD1	CD21	CD41	CD61	CD81
CD2	CD22	CD42	CD62	CD82
CD3	CD23	CD43	CD63	CD83
CD4	CD24	CD44	CD64	CD84
CD5	CD25	CD45	CD65	CD85
CD6	CD26	CD46	CD66	CD86
CD7	CD27	CD47	CD67	CD87
CD8	CD28	CD48	CD68	CD88
CD9	CD29	CD49	CD69	CD89
CD10	CD30	CD50	CD70	CD90
CD11	CD31	CD51	CD71	CD91
CD12	CD32	CD52	CD72	CD92
CD13	CD33	CD53	CD73	CD93
CD14	CD34	CD54	CD74	CD94
CD15	CD35	CD55	CD75	CD95
CD16	CD36	CD56	CD76	CD96
CD17	CD37	CD57	CD77	CD97
CD18	CD38	CD58	CD78	CD98
CD19	CD39	CD59	CD79	CD99
CD20	CD40	CD60	CD80	CD100

「CD19」

　　[★]

関

CD、免疫グロブリン

同

B4

• B-cell co-receptor

• CD19+CD21+CD81

発現細胞

• B細胞

機能

• Forms complex with CD21(CR2) and CD81(TAPA-1); co-receptor for B-cell--cytoplasmic domain binds cytoplasmic tyrosine kinases and PI 3-kinase
• CD21(CR2)にC3dが結合するとCD19の細胞内領域がリン酸化され、Src-family kinase(Lyn etc.)やPI 3-kinaseをリクルートし、PI 3-kinaseは下流にシグナルを伝達する

「CD19:CD21 :CD81」

　　[★]

同

B cell co-receptor complex

同

B cell co-receptor complex

「CD212」

　　[★]

同

Interleukin-12 receptor-β,

「CD210」

　　[★]

同

Interleukin-10 receptor

「CD2」

　　[★]

同

Leucine-5, SRBC receptor, LFA-2

関

CD

発現細胞

• T細胞、胸腺細胞、NK細胞

分子量

• 45-58

機能

• 接着分子、CD58(LFA-3)に結合。細胞内部でLckに結合し、T細胞を活性化

• リンパ球が抗原提示細胞と相互作用するのに重要 (IMM.343)

別名

• LFA-2, T11

ファミリー

• immunoglobulin

「CD」

　　[★]

• 表面抗原分類 cluster of differentiation
• 膠原病 collagen disease
• 集合管 collecting duct
• クローン病 Crohn's disease