Phosphorothioate‐modified C p G oligodeoxynucleotides mimic autoantigens and reveal a potential role for T oll‐like receptor 9 in receptor revision

Re‐expression of recombinase activating genes ( RAG ) in mature B cells may support autoreactivity by enabling revision of the B ‐cell receptor ( BCR ). Recent reports suggest that administration of T oll‐like receptor 9 ( TLR 9) ‐stimulating C p G oligodeoxynucleotides ( ODN ) could trigger the manifestation of autoimmune disease and that TLR are involved in the selection processes eliminating autoreactive BCR . The mechanisms involved remain to be elucidated. This prompted us to ask, whether TLR 9 could be involved in receptor revision. We found that phosphorothioate‐modified C p G ODN ( C p G PTO ) induced expression of K u70 and re‐expression of RAG ‐1 in human peripheral blood B lymphocytes and I gλ expression in sorted I gκ + B cells. Further results revealed unselective binding specificity of C p G PTO ‐induced immunoglobulin and suggested that C p G PTO engage and/or mimic I g M receptor signalling, an important prerequisite for the initialization of receptor editing or revision. Altogether, our data describe a potential role for TLR 9 in receptor revision and suggest that C p G PTO could mimic chromatin‐bearing autoantigens by simultaneously engaging the BCR and TLR 9 on I g M + B cells.