Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL

Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain...

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Bibliographic Details
Authors: Blanco Ares, Gonzalo, 1989-, Vardi, Anna, Puiggros Metje, Anna Maria, Gómez-Llonín, Andrea, Muro, Manuel, Rodríguez-Rivera, María, Stalika, Evangelia, Abella Monreal, Eugenia, Gimeno Vázquez, Eva, López-Sánchez, Manuela, Senín Magan, Maria Alicia, Calvo, Xavier, Abrisqueta, Pau, Bosch José, Francesc Xavier, 1947-, Ferrer Del Alamo, Ana, Stamatopoulos, Kostas, Espinet Solà, Blanca
Format: article
Status:Versión aceptada para publicación
Publication Date:2018
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/41875
Online Access:http://hdl.handle.net/10230/41875
http://dx.doi.org/10.1080/2162402X.2018.1432328
Access Level:Open access
Keyword:T cell receptor (TR)
Antigen restriction
Chronic lymphocytic leukemia (CLL)
Clonotype
Monoclonal B cell lymphocytosis (MBL)
Description
Summary:Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4+ and CD8+ T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4+ T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

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