Table 1.

TLR7/TLR9 responses have substantiated roles in both autoantibody production and autoimmunity, especially in B cell receptor (BCR)-activated B cells.

	TLR7 and TLR9 functions in B cell autoimmunity	Reference
TLR7	RNA-associated antigen recognition	(11)
	RNA-associated autoantibody production	(9)
	Pathogenic role in development of autoimmunity (murine models) Increased IgG production Increased immune (B and T) cell activation Promoted survival of plasmablast/antibody forming cells Increased systemic lupus erythematosus (SLE)-related mortality and pathogenesis	(7, 14, 18, 20)
TLR9	Endogenous double-stranded deoxyribonucleic acid (dsDNA) and chromatin antigen recognition Anti-dsDNA and chromatin-associated autoantibody production	(8, 9, 14)
	Protective role in autoimmunity (by limiting potentially pathogenic role of TLR7 in murine models) Attenuated IgG production (both total and pathologic) Decreased immune activation Induced of B cell tolerance and cell death Decreased SLE-related mortality and pathogenesis	(12, 13, 15–18, 20)
	Functional synergy of BCR–TLR7/TLR9 pathways
BCR–TLR7/TLR9	BCR activation results in increased TLR9	(29)
	BCR dictates subcellular location of TLR9	(28)
	BCR and TLR7/TLR9 increases proliferation, cytokine, and autoantibody production	(25–27, 29, 32)
	BCR and TLR7 operate together to confer autoimmunity, by attenuating TLR7 tolerance	(35)
	BCR and TLR9 synergize to confer central tolerance	(36)
	Proximal BCR-signaling components and TLR7/TLR9 autoimmune responses
	Syk inhibition of B cells blocked the CpG response	(40)
	Btk and Syk mediate TLR crosstalk	(38, 41, 42)
	Btk is dispensible for TLR7 and 9 (ligands and immune complex) proliferation	(39)
	Lyn negatively regulates: Both anti-RNA and anti-dsDNA antibody production (both global deletion and B-cell specific) IgG class-switching B cell activation Cytokine production (pro-inflammatory) Autoimmune pathology	(44–46)