Immunoglobulin gene recombination can result in the assembly of self-reactive antibodies. Deletion, anergy or receptor editing normally silence B cells that produce these autoantibodies. Receptor editing is highly efficient in mouse B cells that carry pre-recombined autoantibody transgenes or gene “knock-ins”. However, it has been difficult to identify cells that have edited receptors in unmanipulated mice and humans. To try to identify such cells we isolated and characterized B cells that coexpress surrogate and conventional 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 evidence of receptor editing. These cells accumulate in the joints of patients with rheumatoid arthritis, consistent with a role for V-preB+L+ B cells and receptor editing in autoimmune disease.
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We thank the Nussenzweig lab for comments and discussions; G. Michel, H. Chambost and C. Fossat for blood samples; W. Muller and K. Tai for tonsil and joint samples and P. Wilson, J. D. Capra and N. Chiorazzi for sharing unpublished data. Supported by grants from the NIH (to M.C.N. and J.W.Y.) and the Leukemia and Lymphoma Society (to J.W.Y.). M.C.N. is based at the Howard Hughes Medical Institute.
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Meffre, E., Davis, E., Schiff, C. et al. Circulating human B cells that express surrogate light chains and edited receptors. Nat Immunol 1, 207–213 (2000). https://doi.org/10.1038/79739
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