Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation

Kseniya S Aulova,Georgy A Nevinsky,Valery P Tereshchenko,Irina A Orlovskaya,Thomas Budde,Andrey E Urusov,Sergei V Sennikov,Yuliya A Shevchenko,Sergey E Sedykh,Ludmila B Toporkova,Sven G Meuth

doi:10.1007/s11033-020-06117-8

Abstract

Exact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.

Highlights

Multiple sclerosis (MS) is pathology of the central nervous system (CNS) associated with the occurrence of increased numbers of macrophages and T lymphocytes
It was shown that spontaneous development of EAE by C57BL/6 mice leads to slow changes during 2–3 months in the hematopoietic stem cells (HSCs) differentiation profiles, and the levels of lymphocyte proliferation in various organs were associated with the production of antibodies against myelin oligodendrocyte glycoprotein (MOG), MBP, and DNA [7,8,9,10]
This leads to the increase in the blood concentration of DNA-histones complexes, which known as the main antigens of mammals leading to the production of Abs against DNA and histones [36,37,38,39,40]

Summary

Introduction

Multiple sclerosis (MS) is pathology of the central nervous system (CNS) associated with the occurrence of increased numbers of macrophages and T lymphocytes. Many studies support the important role of autoimmune (AI) reactions in the destruction of myelin. Several recent publications validate the B cells and autoantibodies (auto-Abs) against myelin autoantigens’ important role in MS pathogenesis [1,2,3]. The increased amounts of auto-Abs and the accumulation of B cells in the cerebrospinal fluid (CSF), together with the typical lesions in MS patients, provide key evidence for the involvement of demyelination to the humoral response [4]. Studies of animal models speak in favor that auto-Abs to myelin components may be involved in Ab-dependent demyelination [3]. Auto-Abs to cell protein-oligodendrocyte progenitors can interfere with remyelination by impeding or removing these cells [5]

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Conclusion