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

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

doi:http://dx.doi.org/10.1080/2162402X.2018.1432328

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

Citation

Blanco G, Vardi A, Puiggros A, Gómez-Llonín A, Muro M, Rodríguez-Rivera M et al. Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL. Oncoimmunology. 2018 Feb 20;7(6):e1432328. DOI: 10.1080/2162402X.2018.1432328

Abstract

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.
This work has been supported by the following grants: PI11/01621, PI15/00437, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness; 2014/SGR585, Generalitat de Catalunya; Fundació La Caixa; H2020 No. 692298 project “MEDGENET, Medical Genomics and Epigenomics Network” by the EU; H2020 “AEGLE, An analytics framework for integrated and personalized healthcare services in Europe”, by the EU.