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Complement receptor 2

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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 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 4,224 coding 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 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 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 follicular dendritic cells 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. ^ a b 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. ^ a b "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, L E (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). UNITED STATES: 2841–50. ISSN 0022-1767. PMID 1383329. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  5. ^ Horváth, G (1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". J. Biol. Chem. 273 (46). UNITED STATES: 30537–43. doi:10.1074/jbc.273.46.30537. ISSN 0021-9258. PMID 9804823. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  6. ^ Yefenof E, Klein G, Jondal M, Oldstone MB (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Jacobson AC, Weis JH (2008). "Comparative functional evolution of human and mouse CR1 and CR2". J. Immunol. 181 (5). UNITED STATES: 2953–9. doi:10.4049/jimmunol.1203176. PMID 18713965. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |month= ignored (help)
  8. ^ Donius LR, Handy JM, Weis JJ, Weis JH (2013). "Optimal Germinal Center B Cell Activation and T-Dependent Antibody Responses Require Expression of the Mouse Complement Receptor Cr1". J. Immunol. 191 (1). UNITED STATES: 434–47. doi:10.4049/jimmunol.1203176. PMID 23733878. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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.

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