Complement Receptor 2 (CD21)

CR2 (complement receptor 2), also known as complement C3d receptor or CD21 (cluster of differentiation 21), is a 140 kDa receptor encoded by the CR2 gene. The common CR2 ligands include complement C3 fragments iC3b, C3dg and C3d, Epstein-Barr virus glycoprotein 350/220, and the immunoregulatory protein CD23. This receptor is found on B cells, thymocytes, follicular dendritic cells, T cells (subset), astrocytes, and pharyngeal epithelial cells and plays a major role in the immune responses through bridging innate and adaptive immunity against foreign pathogens and proteins. Acting as a B cell co-receptor, binding of CR2 to CD19 increases BCR-dependent cell activation. Besides, ligation of CR2 alone has been revealed to lead to BCR-independent phenotypes, including induction of homotypic adhesion, IL-6 generation, and antigen uptake and presentation to T cells. Furthermore, CR2 also plays a crucial role in increasing humoral immunity to T-dependent and T-independent foreign antigens and in mediating T-cell immunity to both autoantigens and non-autoantigens. In addition to the above, CR2 may be involved in innate immunity. It can bind to activators of innate immunity such as IFN-α, an anti-viral cytokine, causing B cell activation. During the development of autoimmunity, CR2 participants in maintaining tolerance to self-antigens. Deficiencies of CR2 are associated with susceptibility to systemic lupus erythematosus (SLE).

Fig.1 Complement receptors. (Merle, 2015)

Reference

1. Merle, N., et al. Complement system part I–Molecular mechanisms of activation and regulation. Frontiers in Immunology. 2015, 6(4):262.