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Early pre-B cells from normal and X-linked agammaglobulinaemia produce Cμ without an attached VH region

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Abstract

Differentiation of B lymphocytes follows an ordered pathway marked by somatic rearrangements of immunoglobulin heavy- and light-chain genes in conjunction with cellular transitions1–4. Although low level constitutive transcription of the μ heavy-chain constant region (Cμ) genes may occur in early precursor cells5, activation of synthesis and translation of complete μ RNA is thought to accompany somatic rearrangements of DNA6. Cytoplasmic μ-chain protein serves as a marker for pre-B cells, the earliest cells committed to differentiation into B lymphocytes4,7,8. μ-chain gene expression in pre-B cells precedes rearrangement and expression of light-chain genes6,8. We now report that early human pre-B cells, Epstein–Barr virus transformed pre-B cells, and pre-B cell hybrid analogues, produce Cμ without the normally associated heavy-chain variable (VH) region. Approximately 5% of normal pre-B cells from adult human bone marrow produce these incomplete μ-chains. Pre-B cells from three patients with X-linked agammaglobulinaemia are exclusively of this immature form, producing Cμ without associated VH. This immune deficiency disease represents a block in differentiation secondary to failure to express VH genes.

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Authors and Affiliations

  1. Children's Hospital Medical Center, Harvard Medical School, 300 Longwood Ave., Boston, Massachusetts, 02115, USA

    Jerrold Schwaber, Stuart H. Orkin & Fred S. Rosen

  2. Department of Pathology, Harvard Medical School, 300 Longwood Ave., Boston, Massachusetts, 02115, USA

    Jerrold Schwaber

  3. Department of Pediatrics, Harvard Medical School, 300 Longwood Ave., Boston, Massachusetts, 02115, USA

    Stuart H. Orkin & Fred S. Rosen

  4. Department of Biophysics, King's College, London, WC2B 5RL, UK

    Harald Molgaard & Hannah J. Gould

Authors
  1. Jerrold Schwaber
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  2. Harald Molgaard
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  3. Stuart H. Orkin
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  4. Hannah J. Gould
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  5. Fred S. Rosen
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Schwaber, J., Molgaard, H., Orkin, S. et al. Early pre-B cells from normal and X-linked agammaglobulinaemia produce Cμ without an attached VH region. Nature 304, 355–358 (1983). https://doi.org/10.1038/304355a0

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  • DOI: https://doi.org/10.1038/304355a0

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