Abstract
Immunization of experimental autoimmune encephalomyelitis (EAE)‐prone C57BL/6 mice with MOG 35‐55 (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.
Highlights
Multiple sclerosis (MS) is characterized by inflammatory and demyelinating conditions in the central nervous system (CNS) as well as perivascular infiltrates composed largely of T lymphocytes and macrophages
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine
Treatment of C57BL/6 mice with MOG leads to reduced weight gain during the first seven days compared to untreated mice, the average weight increased gradually to approximately match the weight of control mice at day 40 (Fig. 1A)
Summary
Multiple sclerosis (MS) is characterized by inflammatory and demyelinating conditions in the central nervous system (CNS) as well as perivascular infiltrates composed largely of T lymphocytes and macrophages. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine Accumulation of clonal B cells in the CSF and lesions of MS patients are among the main lines of evidence for the involvement of a humoural response in demyelination [4]. Current evidence from clinical studies and animal models suggests that auto-Abs against myelin components (involved in antibody-mediated demyelination [3]), as well as auto-Abs against oligodendrocyte progenitor cell protein, which could impair remyelination by eliminating or impeding these cells [5], may play a crucial role in MS immunopathogenesis
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