Circulating human B cells that express surrogate light chains and edited receptors

Immunoglobulin gene recombination can result in the assembly of self-reacti ve antibodies. Deletion, anergy or receptor editing normally silence B cell s that produce these autoantibodies. Receptor editing is highly efficient i n mouse B cells that carry pre-recombined autoantibody transgenes or gene " knock-ins". However, it has been difficult to identify cells that have edit ed receptors in unmanipulated mice and humans. To try to identify such cell s we isolated and characterized B cells that coexpress surrogate and conven tional light chains (V-preB(+)L(+)) from the blood of normal human donors. V-preB(+)L(+) B cells express RAG mRNA, display an unusual heavy and light chain antibody repertoire consistent with antiself reactivity, and show evi dence of receptor editing. These cells accumulate in the joints of patients with rheumatoid arthritis, consistent with a role for V-preB(+)L(+) B cell s and receptor editing in autoimmune disease.