Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice

Xiaoxing Ma, Jane Foster, Boris Sakic

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Autoantibody-mediated compromise of central neurotransmission is a pathogenic mechanism proposed in etiology of neuropsychiatric lupus (NP-SLE). Recent experimental data support the hypothesis that intrathecally-synthesized antibodies play a key role in brain damage and behavioral dysfunction. However, autoantibody-producing plasma cells have not yet been detected in brain tissue. We presently use contemporary immunohistochemical markers and flow cytometry to assess distribution and prevalence of plasma cells and other phenotypes, which infiltrate brains of lupus-prone MRL-lpr mice. The functional status of infiltrates was confirmed by in situ hybridization for TNF-alpha mRNA. Consistent with the notion of breached blood-CSF and blood-brain barriers, CD3+ T-cells (∼ 20% of the mononuclear cell infiltrate) were plentiful in choroid plexuses and commonly seen around blood vessels. The CD138+ plasma cells were restricted to the choroid plexus and stria medullaris of diseased MRL-lpr mice. Although accounting for less than 1% of the total cell infiltrate, CD19+IgM+ B-cells increased with age in brains of MRL-lpr mice. Severe mononuclear cell infiltration was accompanied by splenomegaly and retarded brain growth. The results obtained support the hypothesis of progressive neurodegeneration as a consequence of leukocyte infiltration and intrathecal autoantibody synthesis. Further characterization of neuroactive antibodies and their targets may contribute to a better understanding of brain atrophy and behavioral dysfunction in the MRL model, and potentially in NP-SLE.

Original languageEnglish (US)
Pages (from-to)26-36
Number of pages11
JournalJournal of Neuroimmunology
Volume179
Issue number1-2
DOIs
StatePublished - Oct 2006
Externally publishedYes

Keywords

  • Autoimmunity
  • B-cells
  • Cerebellum
  • Choroid plexus
  • Flow cytometry
  • Hippocampus
  • Immunohistochemistry
  • Lupus
  • MRL mice
  • Neurodegeneration
  • Plasma cells
  • T-cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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