Citations to this article


Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged VHDJH and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb’s reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG+ B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both.


Fabio Ghiotto ... Manlio Ferrarini, Nicholas Chiorazzi


Total citations by year in Crossref

Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 7 1 2 1 3 4 5 6 6 2 2 39
Citation information

Citations to this article in Crossref (39)

Title and authors Publication Year
B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells
V Seda, M Mraz
European Journal of Haematology 2014
The bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach
M Sivina, RJ Kreitman, E Arons, F Ravandi, JA Burger
British Journal of Haematology 2014
Advances in Immunology
AM Avalos, F Meyer-Wentrup, HL Ploegh
Advances in immunology 2014
Chronic lymphocytic leukaemia: could immunological tolerance mechanisms be the origin of lymphoid neoplasms?
R García-Muñoz, L Llorente
Immunology 2014
Does B Cell Receptor Signaling in Chronic Lymphocytic Leukaemia Cells Differ from That in Other B Cell Types?
JR Slupsky
Scientifica 2014
Stereotyped B-cell receptors in chronic lymphocytic leukemia
A Agathangelidis, A Vardi, P Baliakas, K Stamatopoulos
Leukemia & Lymphoma 2014
Cryptic polyreactivity of IgG expressed by splenic marginal zone B-cell lymphoma
A Mahendra, B Gangadharan, S André, M Boudjoghra, F Davi, M Lecerf, C Planchais, SV Kaveri, S Lacroix-Desmazes, JD Dimitrov
Molecular Immunology 2014
CLL B-cell receptors can recognize themselves: alternative epitopes and structural clues for autostimulatory mechanisms in CLL
M Binder, F Muller, M Frick, C Wehr, F Simon, B Leistler, H Veelken, R Mertelsmann, M Trepel
Blood 2013
Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling
MD Minden, R Übelhart, D Schneider, T Wossning, MP Bach, M Buchner, D Hofmann, E Surova, M Follo, F Köhler, H Wardemann, K Zirlik, H Veelken, H Jumaa
Nature 2012
Pathogenesis of Human B Cell Lymphomas *
AL Shaffer, RM Young, LM Staudt
Annual Review of Immunology 2012
Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity
AA Warsame, HC Aasheim, K Nustad, G Troen, A Tierens, V Wang, U Randen, HP Dong, S Heim, A Brech, J Delabie
Blood 2011
Intraclonal diversification of immunoglobulin light chains in a subset of chronic lymphocytic leukemia alludes to antigen-driven clonal evolution
E Kostareli, LA Sutton, A Hadzidimitriou, N Darzentas, A Kouvatsi, A Tsaftaris, A Anagnostopoulos, R Rosenquist, K Stamatopoulos
Leukemia 2010
Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities
N Chiorazzi, M Ferrarini
Blood 2010
High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease
F Palacios, P Moreno, P Morande, C Abreu, A Correa, V Porro, AI Landoni, R Gabus, M Giordano, G Dighiero, O Pritsch, P Oppezzo
Blood 2010
B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406
MP Quiroga, K Balakrishnan, AV Kurtova, M Sivina, MJ Keating, WG Wierda, V Gandhi, JA Burger
Blood 2009
Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells
T Seiler, M Woelfle, S Yancopoulos, R Catera, W Li, K Hatzi, C Moreno, M Torres, S Paul, H Dohner, S Stilgenbauer, MS Kaufman, JE Kolitz, SL Allen, KR Rai, CC Chu, N Chiorazzi
Blood 2009
Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen
LA Sutton, E Kostareli, A Hadzidimitriou, N Darzentas, A Tsaftaris, A Anagnostopoulos, R Rosenquist, K Stamatopoulos
Blood 2009
A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: molecular and computational evidence
N Darzentas, A Hadzidimitriou, F Murray, K Hatzi, P Josefsson, N Laoutaris, C Moreno, A Anagnostopoulos, J Jurlander, A Tsaftaris, N Chiorazzi, C Belessi, P Ghia, R Rosenquist, F Davi, K Stamatopoulos
Leukemia 2009
Chronic lymphocytic leukaemia: An immunobiology approach
E Kostareli, T Smilevska, K Stamatopoulos, A Kouvatsi, A Anagnostopoulos
Srpski arhiv za celokupno lekarstvo 2008
Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia
A Hadzidimitriou, N Darzentas, F Murray, T Smilevska, E Arvaniti, C Tresoldi, A Tsaftaris, N Laoutaris, A Anagnostopoulos, F Davi, P Ghia, R Rosenquist, K Stamatopoulos, C Belessi
Blood 2008
Chronic lymphocytic leukaemia
G Dighiero, TJ Hamblin
The Lancet 2008
Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy
M Muzio, B Apollonio, C Scielzo, M Frenquelli, I Vandoni, V Boussiotis, F Caligaris-Cappio, P Ghia
Blood 2008
Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3
GF Widhopf, CJ Goldberg, TL Toy, LZ Rassenti, WG Wierda, JC Byrd, MJ Keating, JG Gribben, KR Rai, TJ Kipps
Blood 2008
A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation
JI Martín-Subero, R Ibbotson, W Klapper, L Michaux, E Callet-Bauchu, F Berger, MJ Calasanz, CD Wolf-Peeters, MJ Dyer, P Felman, A Gardiner, RD Gascoyne, S Gesk, L Harder, DE Horsman, M Kneba, R Küppers, A Majid, N Parry-Jones, M Ritgen, M Salido, F Solé, G Thiel, HH Wacker, D Oscier, I Wlodarska, R Siebert
Leukemia 2007
Acquired immune-related and inflammatory conditions and subsequent chronic lymphocytic leukaemia
O Landgren, G Gridley, D Check, NE Caporaso, LM Brown
British Journal of Haematology 2007