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

Nature Immunology volume 1, pages 207–213 (2000)Cite this article

Abstract

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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Figure 1: Surrogate light chain cell-surface expression on peripheral blood B cells.
Figure 2: RAG, TdT, V-preB and λ-like gene expression in human peripheral B cell subsets measured by semiquantitative RT-PCR.
Figure 3: RAG-1, RAG-2, TdT and surrogate light chain gene expression in newly emigrated B cells.
Figure 4: Characterization of VH5(D)JH expression in conventional and V-preB+L+ B cells.
Figure 5: κ light chain repertoire in V-preB+L+ and conventional B cells.
Figure 6: V-preB+L+ B cells are overrepresented in rheumatoid synovia.

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Acknowledgements

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samples; W. Muller and K. Tai for tonsil and joint samples and P. Wilson, J. D. Capra and N. Chiorazzi for sharing unpublished data.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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Authors and Affiliations

  1. Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Avenue, New York, 10021, NY, USA

    Eric Meffre & Michel C. Nussenzweig

  2. Howard Hughes Medical Institute, 1230 York Avenue, New York, 10021, NY, USA

    Eric Meffre & Michel C. Nussenzweig

  3. Division of Clinical Sciences, National Cancer Institute Building 10, Room 5A02, National Institutes of Health, 10 Center Drive, MSC 1374, Bethesda, 20892, MD, USA

    Eric Davis & Louis M. Staudt

  4. Centre d'Immunologie de Marseille-Luminy, case 906 , Marseille, 13288, Cedex 09, France

    Claudine Schiff

  5. Department of Medicine and Pediatrics, Mount Sinai Medical Center, 1425 Madison Avenue, Room 1120, New York, 10029, NY, USA

    Charlotte Cunningham-Rundles

  6. Department of Medicine, Hospital for Special Surgery, 535 East 70th Street, New York, 10021, NY , USA

    Lionel B. Ivashkiv

  7. Department of Medicine, Allogenic Bone Marrow Transplant and Clinical Immunology Services, Memorial Sloan-Kettering Cancer Center Weil Medical College of Cornell University, 1275 York Avenue , New York, 10021, NY, USA

    James W. Young

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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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