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

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  • dc.contributor.author Blanco Ares, Gonzalo, 1989-
  • dc.contributor.author Vardi, Anna
  • dc.contributor.author Puiggros Metje, Anna Maria
  • dc.contributor.author Gómez-Llonín, Andrea
  • dc.contributor.author Muro, Manuel
  • dc.contributor.author Rodríguez-Rivera, María
  • dc.contributor.author Stalika, Evangelia
  • dc.contributor.author Abella Monreal, Eugenia
  • dc.contributor.author Gimeno Vázquez, Eva
  • dc.contributor.author López-Sánchez, Manuela
  • dc.contributor.author Senín Magan, Maria Alicia
  • dc.contributor.author Calvo, Xavier
  • dc.contributor.author Abrisqueta, Pau
  • dc.contributor.author Bosch José, Francesc Xavier, 1947-
  • dc.contributor.author Ferrer Del Alamo, Ana
  • dc.contributor.author Stamatopoulos, Kostas
  • dc.contributor.author Espinet Solà, Blanca
  • dc.date.accessioned 2019-06-27T07:33:42Z
  • dc.date.available 2019-06-27T07:33:42Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.abstract 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.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
  • dc.identifier.doi http://dx.doi.org/10.1080/2162402X.2018.1432328
  • dc.identifier.issn 2162-4011
  • dc.identifier.uri http://hdl.handle.net/10230/41875
  • dc.language.iso eng
  • dc.publisher Taylor & Francis
  • dc.relation.ispartof Oncoimmunology. 2018 Feb 20;7(6):e1432328
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/692298
  • dc.rights © This is an Accepted Manuscript of an article published by Taylor & Francis in Oncoimmunology on 2018 Feb, available online: http://www.tandfonline.com/10.1080/2162402X.2018.1432328
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.keyword T cell receptor (TR)
  • dc.subject.keyword Antigen restriction
  • dc.subject.keyword Chronic lymphocytic leukemia (CLL)
  • dc.subject.keyword Clonotype
  • dc.subject.keyword Monoclonal B cell lymphocytosis (MBL)
  • dc.title Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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