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* Division of Rheumatology and Clinical Immunology, Department of Medicine, and
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610; and
Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235
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
Tcr
-/- mutations onto
B6.Sle1 resulting in the absence of circulating B cells
and 
T cells in B6.Sle1.µMT and
B6.Sle1.Tcr-/-, respectively. The
immune phenotypes in these two strains were compared with that of
B6.Sle1 and B6.µMT or
B6.Tcr-/-.
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.Tcr-/- 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.
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