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Do CLL B cells correspond to naive or memory B-lymphocytes? Evidence for an active Ig switch unrelated to phenotype expression and Ig mutational pattern in B-CLL cells

Abstract

Recent work suggests that chronic lymphocytic leukemia (B-CLL) expressing unmutated immunoglobulin V genes could correspond to the proliferation of naive B cells whereas those expressing mutated genes, may correspond to the proliferation of post-germinal center B cells. Current data from gene profiling expression have failed to demonstrate a clear-cut distinction between these two forms of B-CLL disease. In the present study, we have investigated the complete VH nucleotide sequence and the presence of RNA transcripts from different CH domains in 25 B-CLL patients. Our results demonstrate that: (1) expression of IgD is not related to the mutational frequency and activation of the isotype switch pathway; (2) isotype switch, leading to simultaneous expression at the transcriptional and protein level of IgM, IgD, IgG and IgA, occurs in a small percentage of patients, and (3) different mechanisms such as VDJ duplication and trans-splicing or RNA splicing of long nuclear transcript, could be involved in isotype switch. Our results highlight the difficulty in assigning a normal counterpart to B-CLL cells and raise the possibility that a different B cell development pathway, independent from classical germinal centers, might exist in B-CLL.

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Acknowledgements

This work was supported in part by grants from Comisión Honoraria de Lucha contra el Cáncer (No. 089) and CSIC (Universidad de la República, Uruguay). We wish to thank Dr Michelle Goodhardt, and Dr Alejandro Buschiazzo for reviewing this manuscript and Mrs Anne Louise and Mrs Anne-Marie Balazuc for technical assistance in cell sorting experiments.

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Oppezzo, P., Magnac, C., Bianchi, S. et al. Do CLL B cells correspond to naive or memory B-lymphocytes? Evidence for an active Ig switch unrelated to phenotype expression and Ig mutational pattern in B-CLL cells. Leukemia 16, 2438–2446 (2002). https://doi.org/10.1038/sj.leu.2402731

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