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Vλ genes in chronic lymphocytic leukaemia: highly skewed V gene segment usage with similar CDR3 sequences

Leukemia volume 22, pages 1073–1075 (2008)Cite this article

Expression of a single antibody specificity by normal B cells is essential for the normal functioning of the immune system. Naive B cells express germline, unmutated immunoglobulin genes, but B cells that have encountered an antigen and moved through a germinal centre have antibody genes that bear mutations. Specific antigen–antibody interaction can drive proliferation and potentially this is significant in driving the proliferation of B-cell malignancies including chronic lymphocytic leukaemia (CLL). There is a biased VH gene usage in malignant B-cell populations (particularly CLL1, 2), which supports the importance of antibody-specific processes in driving or maintaining this malignancy. About half of all CLL cases have unmutated immunoglobulin genes and this is associated with poor clinical outcome. One allele of VH1–69 in CLL is overexpressed in unmutated cases of CLL3 and the sequence of the CDR3 region, which is important in antigen binding, is identical in a surprisingly high proportion of patients4, 5 again suggesting that antigen-driven processes may be important in leukaemogenesis. There is much less work on the light-chain V gene usage in CLL but there is a biased usage of both κ and λ light chains.6 We have sequenced rearranged VL genes from λ expressing cases of CLL. In distinction to the previous work on Vλ gene usage based on southern European6 or North American populations, our cases are drawn from northern Europe.

We have PCR amplified (see figure legend) and sequenced rearranged Vλ gene segments from DNA extracted from B cells purified from peripheral blood. Eighty-one rearrangements were amplified from CLL and the PCR product was cloned and sequenced. Sequences were compared to those of germline Vλ genes compiled in the IMGT database7 in order to find the most likely Vλ gene, Jλ gene and mutational status.

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Author notes

  1. A Abusedra and R Joshi: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Investigative Sciences, Department of Haematology, Hammersmith Hospital, London, UK

    A Abusedra, R Joshi, A Bybee, J F Apperley & S D Wagner

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  1. A Abusedra
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  2. R Joshi
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  3. A Bybee
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  4. J F Apperley
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  5. S D Wagner
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Correspondence to S D Wagner.

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Abusedra, A., Joshi, R., Bybee, A. et al. Vλ genes in chronic lymphocytic leukaemia: highly skewed V gene segment usage with similar CDR3 sequences. Leukemia 22, 1073–1075 (2008). https://doi.org/10.1038/sj.leu.2405003

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