Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus

Aurélie de Groof, Patrice Hémon, Olivier Mignen, Jacques Olivier Pers, Edward K. Wakeland, Yves Renaudineau, Bernard R. Lauwerys

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone peptides) is key to the development of the disease and is related to T cell intrinsic defects, contributed by genetic susceptibility factors and by extrinsic amplificatory mechanisms, in particular over-stimulation by antigen-presenting cells. We also describe shifts in B cell sub-populations, going from skewed immature B cell populations as an indication of disturbed central and peripheral tolerance checkpoints, to enriched long-lived plasma cells, which are key to persistent autoantibody production in the disease. B cell activation mechanisms in SLE are both T cell-dependent (break of tolerance and production of specific autoantibodies) and -independent (polyclonal B cell activation, production of autoantibodies by long-lived plasma cells). By providing a comprehensive evaluation of B and T cell surface markers in two major mouse models of SLE and a description of their changes before and after disease onset, this review illustrates how the study of lymphoid cell phenotype delivers key information regarding pathogenic pathways and supplies tools to assess the beneficial effects of novel therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalClinical Reviews in Allergy and Immunology
DOIs
StateAccepted/In press - May 13 2017

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Keywords

  • Autoimmunity
  • B cell
  • Flow cytometry
  • Mouse models
  • Systemic lupus erythematosus
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy

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