title: CD1d(hi)CD5+ B cells expanded by GM-CSF in vivo suppress experimental autoimmune myasthenia gravis.
abstract: IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or suppress the development of experimental autoimmune myasthenia gravis (EAMG) has not been studied. In this study, we investigated whether low-dose GM-CSF, which suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of CD1d(hi)CD5(+) B cells would prevent or suppress EAMG. We found that treatment of EAMG mice with low-dose GM-CSF increased the proportion of CD1d(hi)CD5(+) B cells and B10 cells. In vitro coculture studies revealed that CD1d(hi)CD5(+) B cells altered T cell cytokine profile but did not directly inhibit T cell proliferation. In contrast, CD1d(hi)CD5(+) B cells inhibited B cell proliferation and its autoantibody production in an IL-10-dependent manner. Adoptive transfer of CD1d(hi)CD5(+) B cells to mice could prevent disease, as well as suppress EAMG after disease onset. This was associated with downregulation of mature dendritic cell markers and expansion of regulatory T cells resulting in the suppression of acetylcholine receptor-specific T cell and B cell responses. Thus, our data have provided significant insight into the mechanisms underlying the tolerogenic effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro expansion of CD1d(hi)CD5(+) B cells or B10 cells may represent an effective strategy in the treatment of human myasthenia gravis.
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637 sheng1@uchicago.edu.
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637.
authors.forename: Songhua
authors.initials: S
authors.lastname: Quan
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL 60637.
authors.forename: Betty
authors.initials: B
authors.lastname: Soliven
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; C556062:IL10 protein, mouse; D011950:Receptors, Cholinergic; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor