B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity

Owen T.M. Chan, Michael P. Madaio, Mark J. Shlomchik

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

B cells are required for both the expression of lupus nephritis and spontaneous T cell activation/memory cell accumulation in MRL-Fas(lpr) mice (MRL/lpr). Autoimmunity in the MRL/lpr strain is the result of Fas-deficiency and multiple background genes; however, the precise roles of background genes vs Fas-deficiency have not been fully defined. Fas-deficiency (i.e., the lpr defect) is required in B cells for optimal autoantibody expression, raising the possibility that the central role for B cells in MRL/lpr mice may not extend to MRL/+ mice and, thus, to lupus models that do not depend on Fas- deficiency ('polygenic lupus'). To address this issue, B cell-deficient, Fas- intact MRL/+ mice (J(H)D-MRL/+) were created; and disease was evaluated in aged animals (>9 mo). The J(H)D-MRL/+ animals did not develop nephritis or vasculitis at a time when the B cell-intact littermates had severe disease. In addition, while activated/memory CD4+ and CD8+ T cells accumulated in B cell-intact mice, such accumulation was substantially inhibited in the absence of B cells. This effect appeared to be restricted to the MRL strain because it was not seen in B cell-deficient BALB/c mice (J(H)D-BALB) of similar ages. The results indicate that B cells are essential in promoting systemic autoimmunity in a Fas-independent model. Therefore, B cells have an important role in pathogenesis, generalizable to lupus models that depend on multiple genes even when Fas expression is intact. The results provide further rationale for B cell suppression as therapy for systemic lupus erythematosus.

Original languageEnglish (US)
Pages (from-to)3592-3596
Number of pages5
JournalJournal of Immunology
Volume163
Issue number7
StatePublished - Oct 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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