TY - JOUR

T1 - Cell Differentiation and Proliferation in the Bone Marrow and Other Organs of 2D2 Mice during Spontaneous Development of EAE Leading to the Production of Abzymes

AU - Aulova, Kseniya S.

AU - Urusov, Andrey E.

AU - Toporkova, Ludmila B.

AU - Sedykh, Sergey E.

AU - Shevchenko, Juliya A.

AU - Tereshchenko, Valeriy P.

AU - Sennikov, Sergei

AU - Orlovskaya, Irina A.

AU - Nevinsky, Georgy A.

N1 - This research was endorsed by a grant of the Russian Foundation for Basic Research (20-04-00281) and the Russian State-funded budget project of ICBFM SB RAS 0245-2021-0009 (121031300041-4).

PY - 2022/4/1

Y1 - 2022/4/1

N2 - The exact cellular and molecular mechanisms of multiple sclerosis and other autoimmune diseases have not been established. Autoimmune pathologies are known to be associated with faults in the immune system and changes in the differentiation profiles of bone marrow stem cells. This study analyzed various characteristics of experimental autoimmune encephalomyelitis (EAE) in 2D2 mice. Differentiation profiles of six hematopoietic stem cells of bone marrow were found to significantly differ in 2D2 male and female mice during the spontaneous development of EAE. In addition, we found various properties of B and T cells, CD4+ and CD8+ lymphocytes in blood and several organs (bone marrow, spleen, thymus, and lymph nodes) of 2D2 male and female mice to be considerably different. These changes in hematopoietic stem cells differentiation profiles and level of lymphocyte proliferation in various organs of 2D2 mice were found to induce the production of IgGs against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, increasing the number of autoantibodies hydrolyzing these substrates. We compared the changes of these immunological and biochemical parameters in 2D2 mice with those of mice of two other lines (Th and C57BL/6), also prone to spontaneous development of EAE. Some noticeable and even extreme variations were found in the time-related development of parameters between male and female mice of 2D2, Th, and C57BL/6 lines. Despite some differences, mice of all three lines demonstrated the changes in hematopoietic stem cells profiles, lymphocyte content, and production of catalytic autoantibodies. Given that these changes are harmful to mice, we believe them to cause the development of experimental autoimmune encephalomyelitis.

AB - The exact cellular and molecular mechanisms of multiple sclerosis and other autoimmune diseases have not been established. Autoimmune pathologies are known to be associated with faults in the immune system and changes in the differentiation profiles of bone marrow stem cells. This study analyzed various characteristics of experimental autoimmune encephalomyelitis (EAE) in 2D2 mice. Differentiation profiles of six hematopoietic stem cells of bone marrow were found to significantly differ in 2D2 male and female mice during the spontaneous development of EAE. In addition, we found various properties of B and T cells, CD4+ and CD8+ lymphocytes in blood and several organs (bone marrow, spleen, thymus, and lymph nodes) of 2D2 male and female mice to be considerably different. These changes in hematopoietic stem cells differentiation profiles and level of lymphocyte proliferation in various organs of 2D2 mice were found to induce the production of IgGs against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, increasing the number of autoantibodies hydrolyzing these substrates. We compared the changes of these immunological and biochemical parameters in 2D2 mice with those of mice of two other lines (Th and C57BL/6), also prone to spontaneous development of EAE. Some noticeable and even extreme variations were found in the time-related development of parameters between male and female mice of 2D2, Th, and C57BL/6 lines. Despite some differences, mice of all three lines demonstrated the changes in hematopoietic stem cells profiles, lymphocyte content, and production of catalytic autoantibodies. Given that these changes are harmful to mice, we believe them to cause the development of experimental autoimmune encephalomyelitis.

KW - Th and C57BL

KW - 6 EAE mice

KW - development of experimental autoimmune encephalomyelitis (EAE)

KW - hematopoietic stem cells differentiation

KW - lymphocyte proliferation in different organs

KW - catalytic antibodies

KW - MYELIN BASIC-PROTEIN

KW - MULTIPLE-SCLEROSIS

KW - HYDROLYZING ANTIBODIES

KW - CATALYTIC ANTIBODIES

KW - COLONY FORMATION

KW - MOUSE MODELS

KW - B-CELLS

KW - AUTOIMMUNE

KW - SERA

KW - DNA

KW - 2D2

KW - and C57BL/6 EAE mice

KW - Th

KW - Bone Marrow/pathology

KW - Peptide Fragments

KW - Cell Proliferation

KW - Male

KW - Female

KW - Cell Differentiation

KW - Autoantibodies

KW - Encephalomyelitis, Autoimmune, Experimental/pathology

KW - Mice, Inbred C57BL

KW - Myelin-Oligodendrocyte Glycoprotein

KW - Animals

KW - Antibodies, Catalytic

KW - Mice

UR - http://www.scopus.com/inward/record.url?scp=85127886709&partnerID=8YFLogxK

U2 - 10.3390/molecules27072195

DO - 10.3390/molecules27072195

M3 - Article

C2 - 35408594

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 7

M1 - 2195

ER -