TLR9 and Splenomegaly: However, even though anti-DNA specific B cells and antibody titers are reduced in the absence of TLR9, there is an exacerbation of lupus pathogenesis (splenomegaly, nephritis, etc.)and an increase in autoantibodies against RNA-associated antigens (176, 177, 181, 183, 184)—suggesting a negative regulatory or tolerogenic role for TLR9 in the pathogenesis of lupus, by suppressing TLR7-mediated autoimmunity.