CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor Vβ genes

Michael P. Davey, Gordon Starkebaum, Thomas P. Loughran

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown etiology characterized by clonal proliferation of T cells that usually express T-cell receptor (TCR) αβ heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diversity (D) region TCR β-chain genes expressed by CD3+ LGL leukemic cells in an attempt to gain insights into the etiology of this disorder. Twelve patients with LGL leukemia were studied, including seven with both LGL leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown etiology that occurs frequently in patients with LGL leukemia. Clonally expanded T cells that express specific TCR Vβ genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, Vβ expression was determined by PCR using a panel of 22 unique Vβ primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant Vβ gene product was readily apparent in all patients. To confirm that the dominant Vβ gene originated from a clonal expansion, DNA fragments corresponding to the dominant Vβ genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The Vβ and Jβ genes expressed by the leukemic cells showed a pattern of distribution that followed the frequency with which these genes are represented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR β chain were different in all cases. A specific pattern of VDJ usage was not identified for those patients with both LGL leukemia and RA; however, utilization of Vβ-6 by LGL clones (N = 3) was observed only in the setting of RA. These data suggest that leukemic CD3+ LGL cells have been clonally transformed in a random fashion with respect to the TCR β chain.

Original languageEnglish (US)
Pages (from-to)146-150
Number of pages5
JournalBlood
Volume85
Issue number1
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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