The major murine systemic lupus erythematosus susceptibility locus Sle1 results in abnormal functions of both B and T cells

Eric S. Sobel, Minoru Satoh, Yifang Chen, Edward K. Wakeland, Laurence Morel

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Sle1 is a major susceptibility locus in the NZM2410 murine model of systemic lupus erythematosus. When isolated on a C57BL/6 background in the B6.Sle1 congenic strain, Sle1 results in the production of high levels of anti-chromatin IgG Abs, histone-specific T cells, and increased B and T cell activation. We have shown by mixed bone marrow chimeras with allotypic markers that Sle1 is expressed in B cells. Using the same technique, we now show that it is also expressed in T cells. To assess whether Sle1 results in intrinsic defects in B or T cells, we have bred the μMT and Tcrα-/- mutations onto B6.Sle1 resulting in the absence of circulating B cells and αβ T cells in B6.Sle1.μMT and B6.Sle1.Tcrα-/-, respectively. The immune phenotypes in these two strains were compared with that of B6.Sle1 and B6.μMT or B6.Tcrα-/-. Sle1-expressing B cells broke tolerance to chromatin in the absence of T cells, as shown by high levels of anti-ssDNA IgM Abs in B6.Sle1.Tcrα-/- mice, and had an increased expression of activation markers. Conversely, increased expression of activation markers and increased cytokine production were observed in Sle1-expressing T cells in the absence of B cells in B6.Sle1.μMT mice. However, the production of IgG antinuclear Abs required the presence of both T and B cells. These experiments showed that Sle1 expression results in both B and T cells intrinsic defects and demonstrate that the documented involvement of each cell compartment in the production of anti-chromatin Abs corresponds to genetic defects rather than bystander effects.

Original languageEnglish (US)
Pages (from-to)2694-2700
Number of pages7
JournalJournal of Immunology
Volume169
Issue number5
DOIs
StatePublished - Sep 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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