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Failure of receptor revision in the autoreactive B cells in patients with systemic lupus erythematosus
Arthritis Res Ther volume 5, Article number: 30 (2003)
Systemic lupus erythematosus (SLE) is a prototype of autoimmune diseases characterized by B-cell hyper-reactivity and production of various autoantibodies. It has recently been found that the recombination activating gene (RAG) is re-expressed in activated mature B cells, and RAG-expressing B cells revise their surface immunoglobulin or die by failure of productive secondary rearrangement, leading to elimination of the autoreactive B cells. We have investigated the expression of RAG proteins in mature B cells in patients with SLE. Although normal mature B cells did not express RAG proteins spontaneously, activated B cells expressed RAGs. In SLE, whole mature B cells spontaneously expressed RAG proteins excessively. Because we had found that failure of receptor editing of the Vk gene with autoreactive potential (A30-Vk2) is associated with the development of anti-DNA antibody in SLE, we next focused on anti-DNA autoantibody secreting B cells. We found that anti-DNA autoantibody secreting B cells failed to re-express RAGs spontaneously, even after activation with mitogen. Thus, anti-DNA autoantibody secreting B cells did not revise their immunoglobulin gene nor die via apoptosis, leading them to develop and persist with autoantibody secretion. These findings indicate the importance of appropriate RAG re-expression for the elimination of autoreactive B cells even at the mature stage, and the absence of such events in anti-DNA secreting B cells may be important for autoantibody production in SLE.
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Yoshikawa, H., Nagafuchi, H., Kurokawa, M. et al. Failure of receptor revision in the autoreactive B cells in patients with systemic lupus erythematosus. Arthritis Res Ther 5 (Suppl 3), 30 (2003). https://doi.org/10.1186/ar831