Chronic graft-versus-host in Ig knockin transgenic mice abrogates B cell tolerance in anti-double-stranded DNA B cells

Debora R. Sekiguchi, Sandra M. Jainandunsing, Michele L. Fields, Michael A. Maldonado, Michael P. Madaio, Jan Erikson, Martin Weigert, Robert A. Eisenberg

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Anti-dsDNA Abs are specific diagnostic markers of systemic lupus erythematosus, and are also implicated in kidney pathology. Anti-dsDNA B cells have been shown to be tolerized in nonautoimmune mice. The immunodysregulation that causes these cells to break tolerance is presumably part of the fundamental defects in systemic lupus erythematosus. To explore these mechanisms, we used the chronic graft-versus-host model mediated by MHC class II differences. Induction of chronic graft-vs-host in anti-DNA H chain knockin (3H9.KI) transgenic mice on a nonautoimmune background resulted in specific activation of anti-dsDNA B cells, as evidenced by high titers of soluble Ab in sera and a high frequency (70%) of anti-dsDNA B cell clones recovered as hybridomas. In addition, the λ+-anti-dsDNA B cells developed increased expression of cell surface activation markers, and concentrated in the T cell area of the follicle with an Ab-forming cell-compatible phenotype. Genetic analysis of the hybridoma clones showed strong evidence of secondary rearrangements of the L chain associated with anti-dsDNA reactivity. Thus, our study indicates that alloreactive T cell help can break tolerance in a complex manner, involving several events.

Original languageEnglish (US)
Pages (from-to)4142-4153
Number of pages12
JournalJournal of Immunology
Volume168
Issue number8
DOIs
StatePublished - Apr 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sekiguchi, D. R., Jainandunsing, S. M., Fields, M. L., Maldonado, M. A., Madaio, M. P., Erikson, J., Weigert, M., & Eisenberg, R. A. (2002). Chronic graft-versus-host in Ig knockin transgenic mice abrogates B cell tolerance in anti-double-stranded DNA B cells. Journal of Immunology, 168(8), 4142-4153. https://doi.org/10.4049/jimmunol.168.8.4142