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Burkitt’s Lymphoma Is a Malignancy of Mature B Cells Expressing Somatically Mutated V Region Genes

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Abstract

Background

The developmental stage from which stems the malignant B cell population in Burkitt’s lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rearranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells and their descendents.

Materials and Methods

Rearranged Vκ region genes from 10 κ-expressing sporadic and endemic BL-derived cell lines (9 IgM and 1 IgG positive) and three κ-expressing endemic BL biopsy specimens were amplified by polymerase chain reaction and sequenced. In addition, VH region gene sequences from these cell lines were determined.

Results

All BL cell lines and the three biopsy specimens carried somatically mutated V region genes. The average mutation frequency of rearranged Vκ genes from eight BL cell lines established from sporadic BL was 1.8%. A higher frequency (6%) was found in five endemic cases (three biopsy specimens and two BL cell lines).

Conclusions

The detection of somatic mutations in the rearranged V region genes suggests that both sporadic and endemic BL represent a B-cell malignancy originating from germinal center B cells or their descendants. Interestingly, the mutation frequency detected in sporadic BL is in a range similar to that characteristic for IgM-expressing B cells in the human peripheral blood and for μ chain-expressing germinal center B cells, whereas the mutation frequency found in endemic BL is significantly higher.

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Acknowledgments

This work was supported by Deutsche Forschungsgemeinschaft through Di184 and SFB 242. We thank H. G. Zachau for helpful discussions and H. Gustav Klobeck for critical reading of the manuscript.

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Authors and Affiliations

  1. Institute for Genetics, University of Cologne, LFI-Gebäude, E4 R706, Josef-Stelzmannstrasse 9, 50931, Cologne, Germany

    Ulf Klein, Klaus Rajewsky & Ralf Küppers

  2. Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden

    George Klein & Barbro Ehlin-Henriksson

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Klein, U., Klein, G., Ehlin-Henriksson, B. et al. Burkitt’s Lymphoma Is a Malignancy of Mature B Cells Expressing Somatically Mutated V Region Genes. Mol Med 1, 495–505 (1995). https://doi.org/10.1007/BF03401587

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