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Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizion

Author

Listed:
  • Wong Yu

    (Laboratory of Molecular Immunology)

  • Hitoshi Nagaoka

    (Laboratory of Molecular Immunology
    Howard Hughes Medical Institute, the Rockefeller University)

  • Mila Jankovic

    (Laboratory of Molecular Immunology
    Institute for Molecular Genetics and Genetic Engineering)

  • Ziva Misulovin

    (Laboratory of Molecular Immunology
    Howard Hughes Medical Institute, the Rockefeller University)

  • Heikyung Suh

    (Laboratory of Molecular Immunology
    Howard Hughes Medical Institute, the Rockefeller University)

  • Antonius Rolink

    (Basel Institute for Immunology)

  • Fritz Melchers

    (Basel Institute for Immunology)

  • Eric Meffre

    (Laboratory of Molecular Immunology
    Howard Hughes Medical Institute, the Rockefeller University)

  • Michel C. Nussenzweig

    (Laboratory of Molecular Immunology
    Howard Hughes Medical Institute, the Rockefeller University)

Abstract

Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V (D)J -recombination-activating genes (RAGs)1,2,3. Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2 (ref. 4). We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.

Suggested Citation

  • Wong Yu & Hitoshi Nagaoka & Mila Jankovic & Ziva Misulovin & Heikyung Suh & Antonius Rolink & Fritz Melchers & Eric Meffre & Michel C. Nussenzweig, 1999. "Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizion," Nature, Nature, vol. 400(6745), pages 682-687, August.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6745:d:10.1038_23287
    DOI: 10.1038/23287
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    Cited by:

    1. Alexia Borelli & Jérémy C. Santamaria & Cloé Zamit & Cécile Apert & Jessica Chevallier & Philippe Pierre & Rafael J. Argüello & Lionel Spinelli & Magali Irla, 2024. "Lymphotoxin limits Foxp3+ regulatory T cell development from Foxp3lo precursors via IL-4 signaling," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Chen Chen & Bongsoo Park & Emeline Ragonnaud & Monica Bodogai & Xin Wang & Le Zong & Jung-Min Lee & Isabel Beerman & Arya Biragyn, 2022. "Cancer co-opts differentiation of B-cell precursors into macrophage-like cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Emilie J. Cosway & Kieran D. James & Andrea J. White & Sonia M. Parnell & Andrea Bacon & Andrew N. J. McKenzie & W. E. Jenkinson & Graham Anderson, 2023. "The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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