Analysis of RAG expression in antibody-secreting B cell of SLE patients

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We have investigated expression of recombination activating gene (RAG) proteins by peripheral blood mature B lymphocytes of normal subjects and patients with SLE. Although normal B cells did not express RAG proteins spontaneously, activated B cells expressed RAGs. Recombination signal sequence (RSS) binding activity of the RAGs was verified by a gel shift assay. Usage of a most downstream Jκ, Jκ5, was evident in activated B cells expressing RAGs. λ chain and intracellular RAGs were simultaneously expressed on the purified κ+ B cells after activation. Both findings suggest secondary light chain rearrangement in mature B cells. Some of RAG-expressing B cells could have failed in productive secondary rearrangement and they died via apoptosis. Thus, RAG-expressing B cells would revise their surface Ig or would die, leading to elimination of the autoreactive B cells.We found that anti-DNA autoAb secreting B cells in patients with SLE failed to express RAG spontaneously nor even with activation. Thus anti-DNA secreting B cells did not revise their Ig gene nor die via apoptosis, causing them to develop and persist autoAb secretion by SLE B cells. These results suggest that failure of RAG reexpression in anti-DNA secreting B cells may be important for autoAb production of SLE patients.