TY - JOUR

T1 - Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

AU - Aulova, Kseniya S.

AU - Toporkova, Ludmila B.

AU - Lopatnikova, Julia A.

AU - Alshevskaya, Alina A.

AU - Sedykh, Sergey E.

AU - Buneva, Valentina N.

AU - Budde, Thomas

AU - Meuth, Sven G.

AU - Popova, Nelly A.

AU - Orlovskaya, Irina A.

AU - Nevinsky, Georgy A.

N1 - Publisher Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA-methylated bovine serum albumin (met-BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35-55 results in the acceleration of EAE development. Anti-DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7-20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone-DNA results in a reduction of proteinuria, a significant increase in anti-DNA, anti-MBP and anti-MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA-met-BSA only stimulated the formation of anti-DNA antibodies hydrolysing DNA with a long delay (15-20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA-met-BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone-hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time-points. We conclude that MOG, DNA–histone and DNA-met-BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.

AB - Experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA-methylated bovine serum albumin (met-BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35-55 results in the acceleration of EAE development. Anti-DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7-20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone-DNA results in a reduction of proteinuria, a significant increase in anti-DNA, anti-MBP and anti-MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA-met-BSA only stimulated the formation of anti-DNA antibodies hydrolysing DNA with a long delay (15-20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA-met-BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone-hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time-points. We conclude that MOG, DNA–histone and DNA-met-BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.

KW - C57BL/6 mice

KW - catalytic antibodies

KW - colony formation

KW - cytokines

KW - eae model

KW - hematopoietic progenitors differentiation

KW - immunization with DNA–histone complex

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - immunization with DNA-histone complex

KW - COLONY FORMATION

KW - MRL/MPJ-LPR MICE

KW - NECROSIS-FACTOR-ALPHA

KW - MYELIN BASIC-PROTEIN

KW - SUBCLASSES IGG1-IGG4

KW - HYDROLYZING ANTIBODIES

KW - MULTIPLE-SCLEROSIS

KW - AUTOIMMUNE-DISEASES

KW - CATALYTIC HETEROGENEITY

UR - http://www.scopus.com/inward/record.url?scp=85054068317&partnerID=8YFLogxK

U2 - 10.1111/jcmm.13850

DO - 10.1111/jcmm.13850

M3 - Article

C2 - 30265424

AN - SCOPUS:85054068317

VL - 22

SP - 5816

EP - 5832

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 12

ER -