Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

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.
View: Text | PDF
Research Article Article has an altmetric score of 9

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

  • Text
  • PDF
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

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1981 Total
Citations: 2 7 9 10 28 16 11 17 25 18 27 25 48 29 37 31 33 30 36 37 33 35 32 29 30 26 12 1 674
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2004 (35)

Title and authors Publication Year
CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival
S Deaglio, T Vaisitti, L Bergui, L Bonello, AL Horenstein, L Tamagnone, L Boumsell, F Malavasi
Blood 2004
Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia
BT Messmer, E Albesiano, DG Efremov, F Ghiotto, SL Allen, J Kolitz, R Foa, RN Damle, F Fais, D Messmer, KR Rai, M Ferrarini, N Chiorazzi
Journal of Experimental Medicine 2004
Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia
D Capello, A Guarini, E Berra, FR Mauro, D Rossi, E Ghia, M Cerri, J Logan, R Foà, G Gaidano
Leukemia 2004
Ig V region restrictions in human chronic lymphocytic leukemia suggest some cases have a common origin
GR Kolar, JD Capra
Journal of Clinical Investigation 2004
Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia
F Ghiotto, F Fais, A Valetto, E Albesiano, S Hashimoto, M Dono, H Ikematsu, SL Allen, J Kolitz, KR Rai, M Nardini, A Tramontano, M Ferrarini, N Chiorazzi
Journal of Clinical Investigation 2004
Mouse Models of Human Cancer
R Benezra, S Rafii, D Lyden
Mouse Models of Human Cancer 2004
Dendritic cells from chronic lymphocytic leukemia patients are normal regardless of Ig V gene mutation status
D Messmer, G Telusma, T Wasil, BT Messmer, S Allen, KR Rai, N Chiorazzi
Molecular Medicine 2004
Activation of the Wnt signaling pathway in chronic lymphocytic leukemia
D Lu, Y Zhao, R Tawatao, HB Cottam, M Sen, LM Leoni, TJ Kipps, M Corr, DA Carson
Proceedings of the National Academy of Sciences 2004
Recent advances in the molecular biology and immunobiology of chronic lymphocytic leukemia
M Ferrarini, N Chiorazzi
Seminars in Hematology 2004
VH3-21 Gene Usage in Chronic Lymphocytic Leukemia – Characterization of a New Subgroup with Distinct Molecular Features and Poor Survival
G Tobin, O Söderberg, U Thunberg, R Rosenquist
Leukemia & Lymphoma 2004
Biallelic IgH rearrangements in patients with indolent lymphoproliferative disorders: Molecular and practical implications
J Cerny, A Slavickova, A Krepelova, M Trneny, J Karban, P Klener
Journal of Cellular Physiology 2004
Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22-23 deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research
F Bertoni, A Conconi, SB Cogliatti, SF Schmitz, M Ghielmini, T Cerny, M Fey, G Pichert, F Bertolini, M Ponzoni, L Baldini, C Jones, R Auer, E Zucca, F Cavalli, FE Cotter
British Journal of Haematology 2004
IgV gene intraclonal diversification and clonal evolution in B-cell chronic lymphocytic leukaemia
D Bagnara, V Callea, C Stelitano, F Morabito, S Fabris, A Neri, S Zanardi, F Ghiotto, E Ciccone, CE Grossi, F Fais
British Journal of Haematology 2004
CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma
V Franco, AM Florena, S Ascani, M Paulli, M Salvato, SA Pileri
Histopathology 2004
Incidence of novel N-glycosylation sites in the B-cell receptor of lymphomas associated with immunodeficiency
F Forconi, D Capello, E Berra, D Rossi, A Gloghini, M Cerri, G Muti, E Morra, M Paulli, U Magrini, M Lucioni, A Rambaldi, F Lauria, A Carbone, FK Stevenson, G Gaidano
British Journal of Haematology 2004
CD1d is expressed on B-chronic lymphocytic leukemia cells and mediates ?-galactosylceramide presentation to natural killer T lymphocytes
F Fais, F Morabito, C Stelitano, V Callea, S Zanardi, M Scudeletti, P Varese, E Ciccone, CE Grossi
International Journal of Cancer 2004
Analysis of IgVH gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery
M Degan, R Bomben, MD Bo, A Zucchetto, P Nanni, M Rupolo, A Steffan, V Attadia, PF Ballerini, D Damiani, C Pucillo, GD Poeta, A Colombatti, V Gattei
British Journal of Haematology 2004
High expression of Bfl-1 contributes to the apoptosis resistant phenotype in B-cell chronic lymphocytic leukemia
AA Morales, A Olsson, F Celsing, A Österborg, M Jondal, LM Osorio
International Journal of Cancer 2004
The role of stem cell transplantation in chronic lymphocytic leukemia
V Rizouli, JG Gribben
Seminars in Hematology 2004
Novel therapies for chronic lymphocytic leukemia
BH Mavromatis, BD Cheson
Blood Reviews 2004
The Prognostic Value of CD38 Expression and its Quantification in B Cell Chronic Lymphocytic Leukemia (B-CLL)
T Mainou-Fowler, HM Dignum, SJ Proctor, GP Summerfield
Leukemia & Lymphoma 2004
Allelotyping in B-Cell Chronic Lymphocytic Leukemia (B-CLL)
U Novak, A Tobler, MF Fey
Leukemia & Lymphoma 2004
Clinical staging and prognostic markers in chronic lymphocytic leukemia
KR Rai, T Wasil, U Iqbal, N Driscoll, D Patel, D Janson, B Mehrotra
Hematology/Oncology Clinics of North America 2004
Perspectives in chronic lymphocytic leukemia biology and management
G Dighiero
Hematology/Oncology Clinics of North America 2004
Molecular genetics and its clinical relevance
S Stilgenbauer, H Döhner
Hematology/Oncology Clinics of North America 2004
The nature and origin of the B-chronic lymphocytic leukemia cell: a tentative model
F Caligaris-Cappio, P Ghia
Hematology/Oncology Clinics of North America 2004
Current Approach to Diagnosis and Management of Chronic Lymphocytic Leukemia
TD Shanafelt, TG Call
Mayo Clinic Proceedings 2004
Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins
GF 2nd, LZ Rassenti, TL Toy, JG Gribben, WG Wierda, TJ Kipps
Blood 2004
Microarray Gene Expression Profiling of B-Cell Chronic Lymphocytic Leukemia Subgroups Defined by Genomic Aberrations and VH Mutation Status
C Haslinger, N Schweifer, S Stilgenbauer, H Döhner, P Lichter, N Kraut, C Stratowa, R Abseher
Journal of Clinical Oncology 2004
Bcl-6 mutation status provides clinically valuable information in early-stage B-cell chronic lymphocytic leukemia
E Sarsotti, I Marugan, I Benet, MJ Terol, D Sanchez-Izquierdo, M Tormo, F Rubio-Moscardo, JA Martinez-Climent, J García-Conde
Leukemia 2004
Engagement of the B-cell antigen receptor (BCR) allows efficient transduction of ZAP-70-positive primary B-CLL cells by recombinant adeno-associated virus (rAAV) vectors
DM Kofler, H Büning, C Mayr, D Bund, J Baumert, M Hallek, CM Wendtner
Gene Therapy 2004
Prognostic impact of p27KIP1 expression in cyclin D1 positive lymphoproliferative disorders
R Letestu, V Ugo, F Valensi, I Radford-Weiss, J Nataf, V Lévy, JG Gribben, X Troussard, F Ajchenbaum-Cymbalista
Leukemia 2004
Hematopathology in Oncology
WG Finn, LA Peterson
2004
Chronic lymphocytic leukemia: revelations from the B-cell receptor
FK Stevenson, F Caligaris-Cappio
Blood 2004
The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process
BT Messmer, E Albesiano, D Messmer, N Chiorazzi
Blood 2004

← Previous 1 2 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 19 patents
291 readers on Mendeley
See more details