title: B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) thought to be primarily mediated by T cells. However, emerging evidence supports an important role for B cells in the pathogenesis and inhibition of MS. Glatiramer acetate (GA), a Food and Drug Administration-approved drug for the treatment of MS, has a good safety profile. But GA's mechanism of action in MS is still elusive. In this study, we showed that B cells from GA-treated mice increased production of IL-10 and reduced expression of co-stimulatory molecules viz.: CD80 and CD86. B cells from GA-treated mice also diminished proliferation of myelin oligodendrocyte glycoprotein (MOG(35-55)) specific T cells. Purified B cells transferred from GA-treated mice suppressed experimental autoimmune encephalomyelitis (EAE) in recipient mice compared with B cells transferred from mice treated with PBS or ovalbumin. The treatment effect of GA in EAE was abrogated in B cell-deficient mice. Transfer of B cells from GA-treated mice inhibited the proliferation of autoreactive T cells as well as the development of Th1 and Th17 cells but promoted IL-10 production in recipient mice. The number of peripheral CD11b(+) macrophages in recipient mice also decreased after transfer of B cells from GA-treated mice; however, the number of dendritic cells and regulatory T cells remained unaltered. These results suggest that B cells are important to the protective effects of GA in EAE.
authors.affiliation: Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. mrinalini.kala@chw.edu
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Kala
authors.forename: Susan N
authors.initials: SN
authors.lastname: Rhodes
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Piao
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.forename: Denise I
authors.initials: DI
authors.lastname: Campagnolo
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Vollmer
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D000068717:Glatiramer Acetate; D006023:Glycoproteins; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D006023:Glycoproteins; D007166:Immunosuppressive Agents; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; D016212:Transforming Growth Factor beta; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D015847:Interleukin-4; D000068717:Glatiramer Acetate