Letter | Published:

Immunoglobulin heavy-chain switching in pre-B leukaemias

Nature volume 301, pages 340342 (27 January 1983) | Download Citation

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Abstract

Immunoglobulin gene expression is initiated in pre-B cells by rearrangements of heavy-chain variable genes V, D and J, for transcription together with the constant region gene Cμ (refs 1–7). The subsequent joining of light-chain V–J genes in the κ or λ families8,9 leads to formation of complete IgM molecules, which are then expressed on the surface of B cells. Heavy-chain isotype switching has been thought to occur later and to involve CH gene rearrangement via deletion of DNA between a switch site 5′ to Cμ and a switch site 5′ to the downstream Cγ, Cε or Cα gene expressed by a mature plasma cell10–15. On the other hand, isotype switching has been seen in human pre-B-cell leukaemias16,17 and in a murine pre-B-cell line before light-chain gene rearrangements and without Cμ gene deletion18,19. To explore further the isotype switching in pre-B cells, we used monoclonal antibodies in immunofluorescence assays to allow unambiguous assignment of the heavy-chain isotypes expressed by individual leukaemic cells in 11 pre-B-cell leukaemias. Switching in these leukaemic clones invariably led to expression of γ1 heavy-chain and κ light-chain determinants, occasionally together with γ4 and α. These results indicate a nonrandom order for heavy-chain isotype switching and for light-chain isotype expression, and also suggest that a mechanism exists for coordinating the two events.

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Affiliations

  1. The Cellular Immunobiology Unit of the Tumor Institute, Departments of Pediatrics and Microbiology, The Comprehensive Cancer Center, and The Children's Hospital, University of Alabama in Birmingham, Birmingham, Alabama 35294, USA

    • Hiromi Kubagawa
    • , Mitsufumi Mayumi
    • , William M. Crist
    •  & Max D. Cooper

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https://doi.org/10.1038/301340a0

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