Complement component (3d/Epstein Barr virus) receptor 2
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Available structures
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CR2 Gene
RNA expression pattern

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]


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]


Although CR2 is present on all mature B-cells and follicular dendritic cells (FDCs), this only becomes readily apparent 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.[7]


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