TLR7 gene duplication accelerates autoimmunity and promotes nucleolar-specific B cells

Systemic autoimmune diseases such as lupus and scleroderma are characterized by the loss of tolerance to nuclear antigens, but the mechanisms by which specific autoantibodies are selected are unclear. Here we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased towards nucleolar antigens due to a duplication of TLR genes in the pseudoautosomal region that makes them more responsive to TLR7 ligands and augments the Btk-dependent signaling pathway. These findings provide genetic evidence that naturally occurring differences in expression of TLR7 have a dramatic impact on antigen selection in autoimmunity. Keywords: genetic modification, Yaa locus Follicular B cells were isolated from spleen of C57BL/6 male and C57BL/6.Yaa male. Four mice from each group using in this analysis were 2 months old. Dye swab labeled RNA had been done in one mice from each group.