Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach.

Molecular Medicine
Monica ColomboFranco Fais

Abstract

B cell receptor Immunoglobulin (BcR IG) repertoire of Chronic Lymphocytic Leukemia (CLL) is characterized by the expression of quasi-identical BcR IG. These are observed in approximately 30% of patients, defined as stereotyped receptors and subdivided into subsets based on specific VH CDR3 aa motifs and phylogenetically related IGHV genes. Although relevant to CLL ontogeny, the distribution of CLL-biased stereotyped immunoglobulin rearrangements (CBS-IG) in normal B cells has not been so far specifically addressed using modern sequencing technologies. Here, we have investigated the presence of CBS-IG in splenic B cell subpopulations (s-BCS) and in CD5+ and CD5- B cells from the spleen and peripheral blood (PB). Fractionation of splenic B cells into 9 different B cell subsets and that of spleen and PB into CD5+ and CD5- cells were carried out by FACS sorting. cDNA sequences of BcR IG gene rearrangements were obtained by NGS. Identification of amino acidic motifs typical of CLL stereotyped subsets was carried out on IGHV1-carrying gene sequences and statistical evaluation has been subsequently performed to assess stereotypes distribution. CBS-IG represented the 0.26% average of IGHV1 genes expressing sequences, were detected in a...Continue Reading

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Citations

Sep 26, 2020·Experimental Hematology·Paul J HengeveldAnton W Langerak
Jun 28, 2021·Hematology/oncology Clinics of North America·Anita Ng, Nicholas Chiorazzi
Jun 28, 2021·Hematology/oncology Clinics of North America·Elisavet VlachonikolaAndreas Agathangelidis
Jun 3, 2021·Blood·Freda K StevensonThomas J Kipps
Oct 23, 2021·Hematological Oncology·Serena MatisFranco Fais

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Datasets Mentioned

BETA
PRJNA515424

Methods Mentioned

BETA
FACS
PCR

Software Mentioned

Illumina
ChangeO
HighV
Illumina Adaptor
pRESTO
SHazaM R package
QUEST

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