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Research Article Free access | 10.1172/JCI116117

Anomalous rearrangements of the immunoglobulin heavy chain genes in human leukemias support the loop-out mechanism of class switch.

M Laffan and L Luzzatto

Department of Haematology, Royal Postgraduate Medical School, London, United Kingdom.

Find articles by Laffan, M. in: PubMed | Google Scholar

Department of Haematology, Royal Postgraduate Medical School, London, United Kingdom.

Find articles by Luzzatto, L. in: PubMed | Google Scholar

Published December 1, 1992 - More info

Published in Volume 90, Issue 6 on December 1, 1992
J Clin Invest. 1992;90(6):2299–2303. https://doi.org/10.1172/JCI116117.
© 1992 The American Society for Clinical Investigation
Published December 1, 1992 - Version history
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Abstract

Discrete rearrangements of immunoglobulin genes are characteristic of lymphoproliferative diseases of B cells and provide direct evidence of their clonal nature. In addition, because leukemic transformation and growth may amplify B cell clones regardless of selection by antigen, analysis of rearranged Ig genes in leukemic clones may give insight into molecular events taking place during the ontogenesis of normal B cells. We have tested DNA samples from patients with chronic B cell leukemias in search for abnormal rearrangements of the Ig heavy chain gene region. By Southern blot analysis we found an unexpected break in the JH-C mu region in 7 out of 118 cases. Two of these cases were investigated in detail by constructing from each a phage genomic library and isolating the phage clones containing the break points. In both cases the JH-C mu separation was confirmed. Further analysis demonstrated that in both cases the abnormality was an inversion of the Ig heavy chain gene between C mu and one of the C gamma segments. This inversion structure strongly suggests that, as has been demonstrated in murine cell lines and in splenocytes stimulated in vitro, class switching in human B lymphocytes occurs in vivo via a loop-out deletion mechanism. The frequency of abnormal events may be as high as 15%. Our data indicate that a proportion of cases of chronic B cell leukemia arise from a cell which has attempted an Ig class switch.

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