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Abstract

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.

Authors

Fabio Ghiotto ... Manlio Ferrarini, Nicholas Chiorazzi

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Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 6 5 4 6 3 8 10 8 9 6 4 69
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Citations to this article in year 2005 (6)

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The Journal of experimental medicine 2005
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C Belessi, K Stamatopoulos, A Hadzidimitriou, K Hatzi, T Smilevska, N Stavroyianni, F Marantidou, G Paterakis, A Fassas, A Anagnostopoulos, N Laoutaris
Molecular medicine (Cambridge, Mass.) 2005
Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity
M Hervé, K Xu, YS Ng, H Wardemann, E Albesiano, BT Messmer, N Chiorazzi, E Meffre
Journal of Clinical Investigation 2005
Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient mice
VL Tarakanova, F Suarez, SA Tibbetts, MA Jacoby, KE Weck, JL Hess, SH Speck, HW 4th
Journal of virology 2005
Chronic Lymphocytic Leukemia
N Chiorazzi, KR Rai, M Ferrarini
New England Journal of Medicine 2005
Mechanisms of B-cell lymphoma pathogenesis
R Küppers
Nature Reviews Cancer 2005

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