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Citations to this article

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
F Fais, … , M Ferrarini, N Chiorazzi
F Fais, … , M Ferrarini, N Chiorazzi
Published October 15, 1998
Citation Information: J Clin Invest. 1998;102(8):1515-1525. https://doi.org/10.1172/JCI3009.
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Research Article Article has an altmetric score of 9

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

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Abstract

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Authors

F Fais, F Ghiotto, S Hashimoto, B Sellars, A Valetto, S L Allen, P Schulman, V P Vinciguerra, K Rai, L Z Rassenti, T J Kipps, G Dighiero, H W Schroeder Jr, M Ferrarini, N Chiorazzi

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Citations to this article in year 2020 (16)

Title and authors Publication Year
Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies
DG Efremov, S Turkalj, L Laurenti
Cancers 2020
B cell signalling pathways—New targets for precision medicine in chronic lymphocytic leukaemia
SS Skånland, L Karlsen, K Taskén
Scandinavian Journal of Immunology 2020
Celebrating 20 Years of IGHV Mutation Analysis in CLL:
N Chiorazzi, FK Stevenson
2020
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation
BA Bartholdy, X Wang, XJ Yan, M Pascual, M Fan, J Barrientos, SL Allen, JA Martinez-Climent, KR Rai, N Chiorazzi, MD Scharff, S Roa
Blood Advances 2020
B Cell Receptor Immunogenetics in B Cell Lymphomas: Immunoglobulin Genes as Key to Ontogeny and Clinical Decision Making
K Gemenetzi, A Agathangelidis, L Zaragoza-Infante, E Sofou, M Papaioannou, A Chatzidimitriou, K Stamatopoulos
Frontiers in Oncology 2020
Molecular modelling of epitopes recognized by neoplastic B lymphocytes in Chronic Lymphocytic Leukemia
A Lupia, S Mimmi, E Iaccino, D Maisano, F Moraca, C Talarico, E Vecchio, G Fiume, F Ortuso, G Scala, I Quinto, S Alcaro
European Journal of Medicinal Chemistry 2020
Analysis of the Targets and Glycosylation of Monoclonal IgAs From MGUS and Myeloma Patients
A Bosseboeuf, C Seillier, N Mennesson, S Allain-Maillet, M Fourny, A Tallet, E Piver, P Lehours, F Mégraud, L Berthelot, J Harb, E Bigot-Corbel, S Hermouet
Frontiers in immunology 2020
Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients
P Monti, M Lionetti, GD Luca, P Menichini, AG Recchia, S Matis, M Colombo, S Fabris, A Speciale, M Barbieri, M Gentile, S Zupo, M Dono, A Ibatici, A Neri, M Ferrarini, F Fais, G Fronza, G Cutrona, F Morabito
Scientific Reports 2020
Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells
J Shingleton, J Wang, C Baloh, T Dave, N Davis, L Happ, O Jadi, R Kositsky, X Li, C Love, R Panea, Q Qin, A Reddy, N Singhi, E Smith, D Thakkar, SS Dave
Cold Spring Harbor Perspectives in Medicine 2020
Evaluation of Somatic Hypermutation Status in Chronic Lymphocytic Leukemia (CLL) in the Era of Next Generation Sequencing
SK Gupta, DS Viswanatha, KP Patel
Frontiers in Cell and Developmental Biology 2020
Precision Medicine Management of Chronic Lymphocytic Leukemia
R Moia, A Patriarca, M Schipani, V Ferri, C Favini, S Sagiraju, WA Essa, G Gaidano
Cancers 2020
Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
AC Leeksma, P Baliakas, T Moysiadis, A Puiggros, K Plevova, AM der Kevie-Kersemaekers, H Posthuma, AE Rodriguez-Vicente, AN Tran, G Barbany, L Mansouri, R Gunnarsson, H Parker, EV den Berg, M Bellido, Z Davis, M Wall, I Scarpelli, A Österborg, L Hansson, M Jarosova, P Ghia, P Poddighe, B Espinet, S Pospisilova, C Tam, L Ysebaert, F Nguyen-Khac, D Oscier, C Haferlach, J Schoumans, M Stevens-Kroef, E Eldering, K Stamatopoulos, R Rosenquist, JC Strefford, C Mellink, AP Kater
Haematologica 2020
Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach
M Colombo, D Bagnara, D Reverberi, S Matis, M Cardillo, R Massara, L Mastracci, JL Ravetti, L Agnelli, A Neri, M Mazzocco, M Squillario, AN Mazzarello, G Cutrona, A Agathangelidis, K Stamatopoulos, M Ferrarini, F Fais
Molecular Medicine 2020
Chronic Lymphocytic Leukemia-Induced Humoral Immunosuppression: A Systematic Review
E Grywalska, M Zaborek, J Łyczba, R Hrynkiewicz, D Bębnowska, R Becht, B Sosnowska-Pasiarska, J Smok-Kalwat, M Pasiarski, S Góźdź, J Roliński, P Niedźwiedzka-Rystwej
Cells 2020
HLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosis
BV Biderman, EB Likold, AR Abdrakhimova, EA Leonov, EG Khamaganova, AB Sudarikov
2020
Assessing prognosis of chronic lymphocytic leukemia using biomarkers and genetics
R Moia, A Patriarca, AM Mahmoud, V Ferri, C Favini, S Rasi, C Deambrogi, G Gaidano
Expert Opinion on Orphan Drugs 2020

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