Can autoantigens acting as TLR ligands, such as CpG DNA, induce anti-dsDNA antibody production in B cells and recruit 'ignorant' lymphocytes through other mechanisms?

From the Research

Autoantigens and TLR Ligands

• Autoantigens, such as CpG DNA, can act as TLR ligands and induce anti-dsDNA antibody production in B cells 1, 2, 3.
• The activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands is a key step in the development of autoimmune diseases 4.
• TLR9, a receptor for CpG DNA, has been implicated in the activation of autoreactive B cells and the production of anti-dsDNA autoantibodies 1, 2.

Mechanisms of Autoantibody Production

• The production of anti-dsDNA autoantibodies is specifically inhibited in TLR9-deficient lupus-prone mice, indicating a critical role for TLR9 in autoantibody formation in vivo 1.
• TLR9-CpG interaction enhances the production of anti-dsDNA antibody and IL-10 in B cells from patients with active SLE 2.
• CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10 3.

Recruitment of 'Ignorant' Lymphocytes

• RNA-associated autoantigens can activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement, which may recruit 'ignorant' lymphocytes through other mechanisms 5.
• The response to RNA-associated autoantigens is markedly enhanced by IFN-alpha, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE) 5.