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.
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
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 |