Changes in haematopoietic progenitor colony differentiation and proliferation and the production of different abzymes in EAE mice treated with DNA

Kseniya S. Aulova, Ludmila B. Toporkova, Julia A. Lopatnikova, Alina A. Alshevskaya, Sergei V. Sennikov, Valentina N. Buneva, Thomas Budde, Sven G. Meuth, Nelly A. Popova, Irina A. Orlovskaya, Georgy A. Nevinsky

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Immunization of experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice with MOG35-55 (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE-prone mice. In contrast to MOG, immunization with DNA leads to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA and a reduction in abzyme production. Immunization with DNA only resulted in a significant increase in DNase activity over 40 days where it became 122-fold higher than before immunization, and fivefold higher when comparing to the maximal activity obtained after MOG treatment. DNA and MOG immunization had different effects on the differentiation profiles of HSCs, lymphocyte proliferation, and the level of apoptosis in bone marrow and other organs of mice. The data indicate that for C57BL/6 mice, DNA may have antagonistic effects with respect to MOG immunization. The usually fast immune response following MOG injection in C57BL/6 mice is strongly delayed after immunization with DNA, which is probably due to a rearrangement of the immune system following the response to DNA.

Original languageEnglish
Pages (from-to)3795-3809
Number of pages15
JournalJournal of Cellular and Molecular Medicine
Volume21
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • C57BL/6 mice
  • Catalytic antibodies
  • Colony formation
  • EAE model
  • Haematopoietic progenitor differentiation
  • Immunization with DNA
  • haematopoietic progenitor differentiation
  • immunization with DNA
  • catalytic antibodies
  • colony formation
  • Antibodies, Catalytic/biosynthesis
  • Encephalomyelitis, Autoimmune, Experimental/chemically induced
  • Myelin-Oligodendrocyte Glycoprotein/administration & dosage
  • Cell Proliferation
  • Mice, Inbred C57BL
  • Immunization/methods
  • Peptide Fragments/administration & dosage
  • Hematopoietic Stem Cells/cytology
  • DNA/administration & dosage
  • Animals
  • Immunity, Humoral
  • Cell Differentiation
  • Colony-Forming Units Assay
  • Mice
  • AUTOANTIBODIES
  • MRL/MPJ-LPR MICE
  • B-CELLS
  • MYELIN BASIC-PROTEIN
  • HYDROLYZING ANTIBODIES
  • MULTIPLE-SCLEROSIS
  • CATALYTIC ANTIBODIES
  • SERA
  • AUTOIMMUNE
  • DISEASES

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