T cell receptor gene expression in autoimmune mice

Academic Article

Abstract

  • Autoimmunity in mice with the lpr/lpr and gld/gld genotypes is accompanied by profound lymphadenopathy characterized by the presence of a massive expansion of an unusual T cell subset. The abnormal lymph node T cells were found to express TcRβ and TcRα transcripts of expected sizes. There was a 10-fold increase in the 1.3-kb TcRβ transcript and a twofold increase in TcRα gene expression, even though Thy-1 expression was in general similar to controls. A study of T cell receptor expression during ontogeny failed to reveal any striking differences between lpr/lpr and congenic mice. There was a strong correlation between TcRβ expression and c-myb expression; however, there was no necessary association of TcRβ and c-myb expression when various T cell lines were examined. Background genes were found to influence the expression of T cell receptor genes in lpr/lpr mice. AKR-lpr/lpr lymph node cells, but not cells from other lpr/lpr mice or AKR +/+ mice, had the predominance of the 1.0-kb TcRβ transcript, which represents the nonfunctional D-J TcRβ rearrangements. Lymph nodes from MRL-lpr/lpr mice, but not C57BL/6-lpr/lpr or AKR-lpr/lpr mice, were found to express small amounts of the TcRγ transcript. In addition, MRL-lpr/lpr but not C57BL/6-lpr/lpr mice had an age-related decreased in thymic TcRβ expression along with a decrease in thymic c-myb expression. The current study extends the characterization of T cell gene expression abnormalities in peripheral T cells of gld/gld and lpr/lpr and describes certain similarities of these cells to immature thymocytes at a molecular level. Furthermore, it illustrates the complex interactions between 'background genes' and genes responsible for lymphoproliferation, which in concert lead to specific molecular and cellular abnormalities.
  • Published In

    Pubmed Id

  • 26366825
  • Author List

  • Mountz JD; Huppi KE; Seldin MF; Mushinski JF; Steinberg AD
  • Start Page

  • 1029
  • End Page

  • 1036
  • Volume

  • 137
  • Issue

  • 3