T cell receptor gene expression in autoimmune mice

J. D. Mountz, K. E. Huppi, Michael F Seldin, J. F. Mushinski, A. D. Steinberg

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1029-1036
Number of pages8
JournalJournal of Immunology
Volume137
Issue number3
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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