Vital Role of Complement Receptor 2 (CR2/CD21) Along With Other Proteins in the Pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and its pathogenesis is unknown. SLE is regulated by complement receptors, proteins and antibodies such as complement receptor 2 (CR2/CD21), anti-dsDNA antibodies, Cysteine p Guanidine DNA (CpG DNA), toll-like receptor 9 (TLR9), interluekin-6 (IL-6), and interferon(IFN-α). Upon activation of plasmacytoid dendritic cells by bacterial CpG DNA or synthetic CpG ODN, these ligands binds to the cell surface CR2 and TLR9 to generate pro inflammatory cytokines via through NF-kB. In this, binding of these ligands induces releases of IFN-α from the plasmacytoid dendritic cells which further binds to IFN-α 1 & 2 receptors present on B cells. This binding was not completely blocked by an anti-IFNαR1 inhibitory antibody, indicating that the released IFN-α may partially binds to the CR2 present on the surface of B cells. IFN-α and IL-6 released from B cells was partially blocked by anti-CR2 inhibitory mAb171. These studies suggested that the cell surface CR2 partially involved in binding these ligands to generate pro inflammatory cytokines. More importantly these CpG DNA or CpG ODN predominantly binds to the cell surface/cellular TLR9 on B cells in order to induce the release of IL-6 and IFN-α, and other pro-inflammatory cytokines. This review describes how the bacterial CpG DNA/CpG motif/ CpG ODN regulate the innate immune system through B cell surface CR2 and TLR9 in B cell signaling.