The immune repertoire of B-cell malignancies

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The BCR is a vital structure for the development and homeostasis of normal B-lymphocytes. Performing large-scale analysis of immunoglobulin gene sequences of various types of B-cell tumors has allowed us to demonstrate that they often display a remarkably skewed repertoire, strongly suggesting that the BCR also plays an important role in their pathogenesis. Within a European collaborative project, we are currently developing high-throughput BCR sequencing approaches including dedicated user-friendly bioinformatics tools (collaboration with Dr Bernardes, Lab of Computational and Quantitative Biology, UMR 7238, UPMC). We develop a robust methodology which can be implemented in diagnostic laboratories for clinical purposes. High-throughput BCR profiling is also used to investigate the clonal architecture and clonal evolution of several tumors including chronic lymphocytic leukemia, Waldenström macrobulinemia and oculo-cerabral lymphoma, in order to further understand the role of antigen selection in their pathogenesis.