T cell receptor gene expression in autoimmune mice.

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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 TcR beta and TcR alpha transcripts of expected sizes. There was a 10-fold increase in the 1.3-kb TcR beta transcript and a twofold increase in TcR alpha 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 TcR beta expression and c-myb expression; however, there was no necessary association of TcR beta 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 TcR beta transcript, which represents the nonfunctional D-J TcR beta 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 TcR gamma transcript. In addition, MRL-lpr/lpr but not C57BL/6-lpr/lpr mice had an age-related decrease in thymic TcR beta 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.