Genetic dissection of SLE pathogenesis

Adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells

Eric S. Sobel, Chandra Mohan, Laurence Morel, Joel Schiffenbauer, Edward K. Wakeland

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Sle1 is a potent autoimmune susceptibility locus on chromosome 1 originally identified in a genome scan of testcross progeny between the systemic lupus erythematosus-prone NZM2410 strain and C57BL/6. We subsequently produced B6.NZMc1, a congenic strain carrying the NZM2410- derived Sle1 genomic interval on the B6 background and demonstrated that Sle1 mediated the loss of tolerance to chromatin in both the B and T cell compartments. In this communication, we show by adoptive transfer experiments that the autoimmune phenotypes of Sle1 are completely reconstituted in B6 radiation chimeras receiving B6.NZMc1 bone marrow but not by the reciprocal reconstitution, demonstrating that Sle1 is functionally expressed in B cells. In additional experiments, cotransfer of mixtures of bone marrow derived from B6.NZMc1 and nonautoimmune congenic B6 mice carrying allelic T and B cell markers showed that only B cells derived from B6.NZMc1 bone marrow produced anti-chromatin autoantibodies. In contrast, increased expression of CD69 was equivalent in CD4+ T cells derived from either B6.NZMc1 or congenic B6 bone marrow, suggesting that either T cell population could be activated subsequent to loss of tolerance in the B cell compartment. These findings indicate that the expression of Sle1 in B cells is essential for the development of autoimmunity.

Original languageEnglish (US)
Pages (from-to)2415-2421
Number of pages7
JournalJournal of Immunology
Volume162
Issue number4
StatePublished - Feb 15 1999

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Adoptive Transfer
Dissection
B-Lymphocytes
Bone Marrow
T-Lymphocytes
Chromatin
Radiation Chimera
Congenic Mice
Chromosomes, Human, Pair 1
Autoimmunity
Systemic Lupus Erythematosus
Autoantibodies
Genome
Phenotype
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Genetic dissection of SLE pathogenesis : Adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells. / Sobel, Eric S.; Mohan, Chandra; Morel, Laurence; Schiffenbauer, Joel; Wakeland, Edward K.

In: Journal of Immunology, Vol. 162, No. 4, 15.02.1999, p. 2415-2421.

Research output: Contribution to journalArticle

Sobel, Eric S. ; Mohan, Chandra ; Morel, Laurence ; Schiffenbauer, Joel ; Wakeland, Edward K. / Genetic dissection of SLE pathogenesis : Adoptive transfer of Sle1 mediates the loss of tolerance by bone marrow-derived B cells. In: Journal of Immunology. 1999 ; Vol. 162, No. 4. pp. 2415-2421.
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